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Study Objectives
Uterine fibroids, affecting 20-50% of all women ,and are benign tumors that arise from myometrial cells of the uterine smooth muscle tissue. Although most are asymptomatic, fibroids can often cause abnormal uterine bleeding, iron deficiency anemia, pelvic pressure symptoms and pain
Intervention / Treatment
DRUG: Carbetocin
| Inclusion Criteria:
* Women aged 25-50 years old.
* Women who will undergo abdominal myomectomy because of symptomatic stage 3-6 fibroids, according to FIGO staging (Laughlin-Tommaso et al., 2017), with the number of myomas not exceeding five based on the preoperative ultrasonography (US).
Exclusion Criteria:
* Women with previous myomectomy.
* Pregnant and postmenopausal women.
* Women with preoperative hemoglobin concentration <10 g/dL,
* women who are candidate for and choosing vaginal or laparoscopic myomectomy.
* History of preoperative embolization or hormone therapy (GnRH analogues), cervical and broad ligament myoma, number of myomas more than five on preoperative US, myoma FIGO stages 1,2,7 and 8 (Munro et al., 2011)
* Patients with allergy or contraindications to carbetocin or epinephrine, such as coronary artery disease, asthma, epilepsy, migraine, kidney, and hepatic disease. |
Study Objectives
The purpose of this study is to prospectively compare the physiologic response of patients who receive either intravenous gadoxetic acid (Eovist) or intravenous gadobenate dimeglumine (MultiHance).
Intervention / Treatment
DRUG: MRI with Multihance, DRUG: MRI with Eovist
| Inclusion Criteria:
* Patients 18 years old and older
* Patients scheduled for MRI examination at the University of Michigan hospital
* Patients receiving either MultiHance or Eovist contrast agents during their clinical MRI examination
Exclusion Criteria:
* Patients under 18 years of age
* Patients who will not receive MultiHance or Eovist as part of their clinical MRI examination |
Study Objectives
The study is divided into two parts. The first part of the study will test various doses of ASN007 to find out the highest safe dose to test in five specific groups. The second part of the study will test how well ASN007 can control cancer.
Intervention / Treatment
DRUG: ASN007: ascending doses, DRUG: ASN007 RD
| Inclusion Criteria:
* Written informed consent obtained prior to any study-related procedure being performed;
* Male or non-pregnant, non-lactating female patient at least 18 years of age at the time of consent;
* Eastern Cooperative Oncology Group Performance Status 0-1 (Part A) and PS 0-2 (Part B)
* Histologically or cytologically confirmed
* advanced or metastatic solid tumor (Part A)
* Group 1: BRAF mutant melanoma (Part B)
* Group 2: NRAS or HRAS mutant solid tumors(Part B)
* Group 3: KRAS mutant CRC.(Part B)
* Group 4: KRAS mutant NSCLC (Part B)
* Group 5: Pancreatic Ductal Adenocarcinoma (Part B)
* Progressive disease after failure of or intolerant to all available standard systemic treatments that have shown a documented benefit in overall survival for their respective tumor type.
* Measurable or evaluable disease per RECIST v*1
* Screening hematology values of the following:
* absolute neutrophil count ≥ 1000/μL,
* platelets ≥ 100,000/μL,
* hemoglobin ≥ 9 g/dL
* Screening chemistry values of the following:
* alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ *0 × upper limit of the normal (ULN),
* total bilirubin ≤ *5 × ULN,
* creatinine ≤ *5 × ULN,,
* albumin ≥ *8 g/dL.
* Screening heart function lab test
* creatinine kinase - MB, troponin-I, and troponin-T within normal limits
* Subject is willing and able to comply with all protocol required visits and assessments, including biopsy if assigned.
Exclusion Criteria:
* Prior treatment with ASN007 or another ERK1/2 inhibitor
* Known hypersensitivity to ASN007 or its excipients;
* Part B: Prior treatment with a RAF or MEK pathway inhibitor, except BRAFmutant melanoma (Group 1)
* Prior chemotherapy, targeted therapy or monoclonal antibody therapy within 3 weeks of start of study treatment (Day1), or 5 half-lives, whichever is shorter.
* Concurrent or prior bone marrow factors (e.g. G-CSF, GM-CSF or erythropoietin) within 3 weeks prior to Day 1 of treatment.
* Febrile neutropenia or serious persistent infection within 2 weeks prior to Day 1 of treatment
* Failure to recover from major surgery or traumatic injury within 4 weeks or minor surgery within 2 weeks prior to Day 1 of treatment.
* History of or current evidence / risk of retinal vein occlusion (RVO) central serous retinopathy (CSR), or glaucoma with intraocular pressures ≥ 21 mmHg or other pre-existing ocular conditions that may put the patient at risk for ocular toxicities
* Known central nervous system (CNS) primary tumor, CNS metastases or carcinomatous meningitis (Part A). Patients may be enrolled with CNS metastasis in certain circumstances in Part B.
* Clinically significant heart disorders including an ejection fraction of < 50%
* Other serious uncontrolled conditions such as fungal, bacterial or viral infection; HIV, Hepatitis B or C, bleeding disorders, interstitial lung disease,
* Any other condition that might place the patient at undue risk. |
Study Objectives
Phase 1 safety, pharmacokinetics, and pharmacodynamics trial of the focal adhesion kinase (FAK) inhibitor PF-00562271 in patients with positive Positron Emission Tomography \[PET\] scans due to advanced non-hematologic malignancies, including pancreatic, head and neck, and prostatic neoplasms, and patients with other malignancies appropriate for serial biopsy. Screening consists of a Fluorodeoxyglucose Positron Emission Tomography \[FDG-PET\] and tumor imaging, medical history, physical examination, Eastern Cooperative Oncology Group \[ECOG\] performance status, blood draws, a pregnancy test for female patients of childbearing potential. Treatment consists of PF00562271 tablets continued until progression of disease, unacceptable toxicity, or patient request. Evaluations for bioactivity are measured by serial FDG-PET and blood tests for biomarkers related to FAK and PYK2 kinase activities.
Intervention / Treatment
DRUG: PF00562271, DRUG: PF00562271, DRUG: PF00562271, DRUG: PF00562271
| Inclusion Criteria:
* Pancreatic, head and neck, and prostatic neoplasms, and patients with non-hematologic malignancies who have tumor appropriate for serial biopsy.
* Adequate organ function, including bilirubin less than *5 x ULN, and \[Eastern Cooperative Oncology Group\] ECOG performance status of 0-*
Exclusion Criteria:
* Clinically significant gastrointestinal abnormalities, requirement for systemic anticoagulants or potent CYP 3A4 inhibitors, and history of clinically significant cardiac or pulmonary disorders. |
Study Objectives
This phase II trial studies the side effects and best dose of capecitabine when given together with pembrolizumab and bevacizumab, and investigates how well they work in treating patients with microsatellite stable colorectal cancer that has spread to nearby tissues or lymph nodes, has spread to other places in the body, or that cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab and bevacizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving capecitabine together with pembrolizumab and bevacizumab may work better in treating patients with colorectal cancer.
Intervention / Treatment
BIOLOGICAL: Bevacizumab, DRUG: Capecitabine, OTHER: Laboratory Biomarker Analysis, BIOLOGICAL: Pembrolizumab
| Inclusion Criteria:
* Have histologically confirmed, locally advanced unresectable or metastatic (stage IV) colorectal adenocarcinoma
* Have locally confirmed MSS or pMMR CRC; MSS is defined as 0-1 allelic shifts among 3-5 tumor microsatellite loci using a PCR-based assay; pMMR is defined as presence of protein expression of 4 MMR enzymes (MLH1, MSH2, MSH6 and PMS2) by immunohistochemistry
* Have stable disease or progression on a prior regimen containing infusional 5-FU or capecitabine according to the interpretation of the treating provider
* Be willing and able to provide written informed consent/assent for the trial
* Be 18 years of age on day of signing informed consent
* Have measurable disease based on RECIST *1
* Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion (phase II dose expansion cohort only); newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor
* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
* Demonstrate adequate organ function performed within 10 days of treatment initiation as defined below:
* Absolute neutrophil count (ANC) >= 1,500 /mcL
* Platelets >= 100,000 / microliter (mcL)
* Hemoglobin >= 9 g/dL or >= *6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
* Serum creatinine =< *5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 60 mL/min for subject with creatinine levels > *5 X institutional ULN. Glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)). Creatinine clearance should be calculated per institutional standard
* Serum total bilirubin =< *5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > *5 ULN. Patients with Gilbert's disease may be included if their direct bilirubin is ≤ *5 X ULN.
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)) =< *5 X ULN OR =< 5 X ULN for subjects with liver metastases
* Albumin >= *5 mg/dL
* International normalized ratio (INR) or prothrombin time (PT) =< *5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
* Activated partial thromboplastin time (aPTT) =< *5 X ULN unless subject is receiving anticoagulant therapy; as long as PT or PTT is within therapeutic range of intended use of anticoagulants
* Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
* Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy
* Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
Exclusion Criteria:
* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
* Has a known history of active tuberculosis (TB) (Bacillus Tuberculosis)
* Hypersensitivity to pembrolizumab or any of its excipients
* Hypersensitivity/intolerance to capecitabine, Infusional 5-Fluorouracil (5-FU), or bevacizumab
* Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
* Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
* Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
* Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
* Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
* Has known history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease.
* Has an active infection at the time of cycle 1 day 1 requiring systemic therapy
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
* Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
* Has known active hepatitis B (e.g., hepatitis B surface antigen (HBsAg) reactive) or hepatitis C (e.g., hepatitis C virus (HCV) ribonucleic acid \[RNA\] \[qualitative\] is detected)
* Requires therapeutic anticoagulation with warfarin at baseline. Patients must be off warfarin or warfarin-derivative anti-coagulants for at least 7 days prior to starting study drug, however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed
* Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug
* Known bleeding risk including serious hemorrhage or hemoptysis within the last 3 months; major surgery within the past 8 weeks or minor surgery within the past 4 weeks
* Has known gastrointestinal bleeding or any other hemorrhage/bleeding event Common Terminology Criteria for Adverse Events (CTCAE) grade > 3 within 6 months of start of study drug
* Has greater than 1+ proteinuria on a urine dipstick or equivalent routine laboratory analysis will require further testing with a urine protein to creatinine ratio (UPCR); UPCR must be calculated as follows: UPCR = protein concentration (mg/dL)/creatinine (mg/dL); if the UPCR >= 1, then the patient will not be eligible for study entry; however, if urinalysis or equivalent routine laboratory analysis shows no protein, then UPCR testing is not required
* Has a history of non-healing wounds or ulcers, or bone re-fractures within 3 months of fracture
* Has a history of arterial thromboembolism within 12 months of start of study drug
* Has inadequately controlled hypertension (defined as systolic blood pressure greater than 150 mm Hg or diastolic blood pressure greater than 95 mm Hg). The use of anti-hypertensive medications to control blood pressure is permitted. Retesting is permitted.
* Has a history of hypertensive crisis or hypertensive encephalopathy within 6 months prior to planned start of study drug
* Has had clinically significant cardiovascular disease within 12 months of planned start of study drug, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
* Has a known history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to planned start of study drug
* Known reversible posterior leukoencephalopathy syndrome (RPLS)
* Difficulty swallowing, malabsorption, active partial or complete bowel obstruction, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of capecitabine
* Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed. |
Study Objectives
Mocetinostat is an orally administered histone deacetylase (HDAC) inhibitor. Azacitidine is a hypomethylating agent (HMA) used to treat MDS. In this study, patients with intermediate- or high-risk MDS will receive treatment with mocetinostat and azacitidine to evaluate the safety of the study treatment. Safety assessments will include echocardiograms, electrocardiograms and routine safety laboratory studies (hematology and serum chemistry). In addition, clinical response to treatment will be monitored using bone marrow aspirates or biopsies, and other routine methods.
Intervention / Treatment
DRUG: Mocetinostat, DRUG: Azacitidine
| Inclusion Criteria:
Diagnosis of intermediate- or high-risk (IPSS criteria) myelodysplastic syndrome.
Cohort 1: Any prior treatment, enrollment complete. Cohort 2: Limited or no prior treatment for MDS. Prior treatment should not include hypomethylating agents such as azacitidine or decitabine, or HDAC inhibitors.
ECOG Performance Status 0 or *
Exclusion Criteria:
Current or history of small, moderate or large pericardial effusion, tamponade and/or pericarditis.
Significant cardiac abnormalities such as recent myocardial infarction, congestive heart failure ≥ Class 3, or symptomatic, uncontrolled atrial fibrillation, atrial flutter or sinus tachycardia.
Prolonged QT/QTc interval.
Other active cancer excluding basal cell carcinoma or cervical intraepithelial neoplasia. |
Study Objectives
This is a single-arm prospective trial of an intra- and postoperative topical antiseptic bundle. The study will recruit patients undergoing an open surgical resection of the upper aerodigestive tract requiring a planed vascularized reconstruction, which may be either pedicled and/or free flap. The objectives are to evaluate antimicrobial effects of a perioperative topical antiseptic bundle and to identify the source of surgical site infection as well as the rate of 30-day adverse events in head and neck cancer.
Intervention / Treatment
DRUG: Chlorhexidine Gluconate, DRUG: Povidone-iodine, DRUG: Tetracycline Ointment
| Inclusion Criteria:
* Age 18 years or older.
* Planned to undergo an open surgical procedure requiring a communication between the upper aerodigestive tract and cervical skin with a planned vascularized reconstruction, which may be either a regional pedicled and/or free flap.
* Subsites reconstructed must include at least one of the following: oral cavity, oropharynx, larynx, hypopharynx, and/or cervical esophagus.
* Eligible patients must be undergoing surgery related to treatment for head and neck cancer. This includes immediate reconstruction after tumor ablation as well as reconstruction for delayed cancer-related indications including radionecrosis or improvement in functional outcomes after head and neck cancer treatment.
* Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
Exclusion Criteria:
* True allergy to any study-related medications
* Active infection at the time of surgery
* Pregnancy or actively breastfeeding mothers. Female subjects who are both lactating and breastfeeding or of childbearing potential who have a positive serum test during screening.
* Patients incarcerated in state or federal penitentiaries
* Patients with a serious medical or psychiatric illness likely to interfere with participation in this clinical study. |
Study Objectives
This is a Phase 1, open-label, multicenter study evaluating the safety and PK profile of ABT-199 under a once daily dosing schedule. Two arms will be implemented for dose escalation: Arm A, CLL/SLL subjects and Arm B, NHL subjects. Arm A is designed to enroll approximately 116 subjects with relapsed or refractory CLL or SLL and Arm B is designed to enroll approximately 95 subjects with relapsed or refractory NHL. Fifty-six subjects were enrolled in Arm A and approximately 55 subjects will be enrolled in Arm B during the dose escalation portion of the study, with the objective of defining dose limiting toxicities (DLTs) and the MTD. Once the MTD is declared for the arm, approximately 60 additional CLL/SLL subjects in Arm A and approximately 20 additional DLBCL subjects and 20 additional follicular lymphoma subjects in Arm B will be enrolled in an expanded safety portion of the study at the recommended phase 2 dose (RPTD) and schedule.
Intervention / Treatment
DRUG: ABT-199
| Inclusion Criteria:
* Subject must have either:
* (Arm A) relapsed or refractory CLL/SLL and require treatment in the opinion of the Investigator. Subject must have relapsed following or be refractory to standard treatments such as fludarabine based regimens (F, FC, FR, FCR) or alkylator (chlorambucil, bendamustine) based regimens. In addition, there are no other curative options, and the subject has exhausted options that would be considered standard of care, or
* (Arm B) relapsed or refractory NHL and require treatment in the opinion of the Investigator. Subject must have histologically documented diagnosis of NHL as defined in the World Health Organization classification scheme, except as noted in the exclusion criteria. Subject must have relapsed following or be refractory to standard treatments such as R-CHOP, R-CVP, or fludarabine based regimens. In addition, there are no other curative options, and the subject has exhausted options that would be considered standard of care. Subjects with other lymphoproliferative diseases can be considered in consultation with the Abbott medical monitor.
* Subject has an Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to *
* Subject must have adequate bone marrow independent of growth factor support per local laboratory reference range at Screening.
* Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening.
Exclusion Criteria:
* CLL subject has undergone an allogeneic or autologous stem cell transplant or NHL subject has undergone an allogeneic stem cell transplant or has been diagnosed with Post-Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia.
* Subject has tested positive for HIV.
* Subject has a cardiovascular disability status of New York Heart Association Class greater or equal to * Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity, results in fatigue, palpitations, dyspnea or anginal pain.
* Subject has a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the Investigator would adversely affect his/her participating in this study.
* Subject has received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug. |
Study Objectives
Study of Plitidepsin in combination with dexamethasone versus dexamethasone alone in patients with relapsed/refractory multiple myeloma.
Intervention / Treatment
DRUG: Plitidepsin, DRUG: Dexamethasone
| Inclusion Criteria:
* Age ≥ 18 years.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
* Life expectancy ≥ 3 months.
* Patients previously diagnosed with multiple myeloma
* Patients must have relapsed or relapsed and refractory multiple myeloma (MM) after at least three but not more than six prior therapeutic regimens for MM, including induction therapy and stem cell transplant in candidate patients, which will be considered as only one regimen.
* Patients must have received previous bortezomib-containing and lenalidomide-containing regimens (or thalidomide where lenalidomide is not available)
* Women must have a negative serum pregnancy test
* Voluntarily signed and dated written informed consent
Exclusion Criteria:
* Concomitant diseases/conditions
* Women who are pregnant or breast feeding.
* Concomitant medications that include corticosteroids, chemotherapy, or other therapy that is or may be active against MM
* Known hypersensitivity to any involved study drug or any of its formulation components |
Study Objectives
This randomized phase II/III trial studies how well netupitant and palonosetron hydrochloride works in preventing chronic nausea and vomiting in patients with cancer. Netupitant and palonosetron hydrochloride may reduce nausea and vomiting.
Intervention / Treatment
DRUG: Netupitant, DRUG: Palonosetron, DRUG: Palonosetron Hydrochloride, OTHER: Placebo, OTHER: Questionnaire Administration
| Inclusion Criteria:
* Diagnosis of cancer
* Chronic nausea over the past 4 weeks
* Average nausea numeric rating scale >= 4/10 over the past 5 days at screening
* Outpatient at MD Anderson Cancer Center
* Karnofsky performance status >= 50%
* Age 18 or older
* Able to complete study assessments, including keeping a daily diary
Exclusion Criteria:
* Delirium (i.e. Memorial Delirium Rating Scale > 13)
* Clinical evidence of bowel obstruction at the time of study enrollment
* Expected to use other 5HT3 antagonists or NK1 antagonists for prophylaxis during the study
* Continuation of over-the-counter therapies for nausea and/or vomiting during the study
* On cytotoxic chemotherapy in the high/moderate/low emetogenic risk categories or oral antineoplastic agents in the high or moderate emetogenic risk categories according to the latest National Comprehensive Cancer Network (NCCN) guideline within 2 weeks of study enrollment
* On scheduled potent CYP3A4 inducers at the time of study enrollment (avasimibe, carbamazepine, phenytoin, rifampin, efavirenz, nevirapine, barbiturates, systemic glucocorticoids, modafinil, oxcarbazine, phenobarbital, pioglitazone, rifabutin, St. John's wort, troglitazone)
* On scheduled CYP3A4 substrates with narrow safety range at the time of study enrollment (alfentanil, cyclosporine, dihydroergotamine, ergotamine, pimozide, quinidine, sirolimus, tacrolimus)
* On scheduled strong or moderate CYP3A4 inhibitors (boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole; amprenavir, aprepitant, atazanavir, ciprofloxacin, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil) within one week of study enrollment
* Unwilling to provide informed consent
* Severe renal impairment (calculated creatinine clearance =< 29 cc/min)
* Calculated creatinine clearance can be done within 14 days of study enrollment
* Severe liver impairment (Child-Pugh score > 9)
* Total (T.) bilirubin, albumin, prothrombin time, and serum creatinine tests can be done within 14 days of study enrollment (only if not performed in the last 14 days)
* Females who are pregnant, lactating, or intend to become pregnant during the participation of the study; childbearing age women who are not on birth control; positive pregnancy test for women of childbearing potential, as defined by intact uterus and ovaries, and no history of menses within the last 12 months; pregnancy test to be performed on the day of enrollment; in cases of women with elevated beta-human chorionic gonadotropin (b-HCG), these candidates will be eligible to participate so long as the level of b-HCG is not consistent with pregnancy and the non-pregnant status is confirmed by a gynecologic examination |
Study Objectives
This is a two-arm, open-label study that aims to compare the incidence and severity of the most common adverse reactions, particularly contact dermatitis, when Valchlor is used alone or in conjunction with triamcinolone ointment 0.1% in early stage MF subjects (Stage IA and IB) for a period of 4 months.
Intervention / Treatment
DRUG: Triamcinolone, DRUG: Valchlor 0.016 % Topical Gel
| Inclusion Criteria:
* Be eligible to receive Valchlor therapy.
* Be at least of 18 years of age and ability to give informed consent
* Have stage IA or IB CTCL
* Subjects with histologic variants of Mycosis Fungoides such as folliculotropic, granulomatous slack skin, syringotropic MF, or large cell transformation ARE eligible.
* A skin biopsy within the last 60 days before start of treatment. In cases with equivocal histological features, the diagnosis may be confirmed with clinicopathologic and/or genetic testing consistent with the National Comprehensive Cancer Network guidelines for Mycosis Fungoides. If sufficient tissue is not available to perform genetic testing, a new biopsy will be performed even if the subject has had a biopsy within 60 days of start of treatment.
* Females of child bearing potential must agree to use two highly effective methods of contraception (strongly recommended that one of the two forms of contraception be non-hormonal such as condom plus spermicide, condom plus diaphragm with spermicide, or have a vasectomized partner) or use an intrauterine device until 30 days after the last day of drug administration. Perimenopausal women must be amenorrhoeic for at least 12 months to be considered of nonchildbearing potential.
* Males with female partners of child bearing potential must agree to sexual abstinence or use two reliable forms of effective contraception simultaneously (strongly recommended that one of the two forms should be non-hormonal as described above) during the entire treatment period and 30 days after the last dose.
* Must be able to comply with the study instructions, apply the study medication as directed, and attend all visits.
* Willingness to avoid sun exposure and ultraviolet B light in areas to be treated.
Exclusion Criteria:
* Have been treated with topical mechlorethamine within 6 months in lesions followed during this study.
* Have received any topical therapy directed against MF within 2 weeks of start of treatment in areas intended to be treated in this study.
* Have received any systemic therapy (oral or injectables) within 3 weeks of start of treatment.
* Not have any intercurrent illness or infection that would interfere with study participation
* Known hypersensitivity to mechlorethamine or triamcinolone.
* Breastfeeding, pregnancy, or intention to become pregnant. |
Study Objectives
Immune therapy represents a promising option for the treatment of an increasing number of malignancies. New immunotherapeutic strategies are currently under development and will be further studied starting from refractory settings of heavily pre-treated mCRC patients. On this basis, a specific immunological characterization of CRC metastasis will be relevant to direct future clinical and pharmacological research.
As surgery is a therapeutic option in the treatment of mCRC, a percentage of mCRC patients undergo to resection of metastasis before or after medical treatment. These tumour samples could be useful to define the immune signature of colorectal metastatic disease.
On the basis of the above reported considerations, an exploratory, prospective, observational study for the immunophenotypical characterization of colorectal cancer metastasis from pre-treated vs chemo-naive patients has been planned.
Intervention / Treatment
| Inclusion Criteria:
* Histological diagnosis of colorectal cancer
* Metastatic disease
* Surgery for metastatic disease
* Availability of clinical data
Exclusion Criteria:
* Non-metastatic disease |
Study Objectives
The investigators propose to study the efficacy of adalimumab versus placebo (double-blind randomization on inclusion into 2 equal groups) on reduction of ocular inflammation quantified by laser flare photometry after two months of treatment in patients with active uveitis despite well conducted treatment with steroid eye drops and MTX. The primary objective is to demonstrate a higher response rate at 2 months in the adalimumab arm versus the placebo arm. Will be considered as responding patients those in whom the evaluated eye, 2 months after inclusion, presents at least 30% reduction of inflammation on laser flare photometry and improvement or a stable appearance on slit lamp examination. After the second month, all patients wishing to continue the trial and presenting a satisfactory clinical state will be treated with adalimumab for a total of one year after inclusion to descriptively evaluate the efficacy and safety of treatment over 10 to 12 months.
Intervention / Treatment
DRUG: Anti-tumor necrosis factor alpha monoclonal antibody, DRUG: placebo
| Inclusion Criteria:
* Active uveitis associated with juvenile idiopathic arthritis, with the exclusion of systemic JIA, juvenile-onset rheumatoid arthritis, and enthesitis-related JIA
* Uveitis resistant to well conducted topical steroid therapy comprising either dexamethasone or rimexolone at a dose adapted to the patient's situation as validated by one of the investigating ophthalmologists.
* Failure of systemic treatment with methotrexate at a dose of *3 to *6 mg.kg (without exceeding 25 mg) once a week for at least 3 months (except in the case of methotrexate intolerance).
* Patient who can be evaluated by laser flare photometry.
* Patient at least 4 years old on initiation of trial medication and weighing a minimum of 15 kg
* Signed informed consent both parents and/or patient's agreement
* Patient has a social security or similar
Exclusion Criteria:
* Systemic JIA, juvenile-onset rheumatoid arthritis, enthesitis-related JIA (with a risk of red eye uveitis).
* History of treatment with anti-TNF alpha monoclonal antibody (either adalimumab or infliximab).
* Any contraindication to administration of immunosuppressive therapy (immune deficit, opportunistic infection, other severe chronic disease)
* History of cancer or lymphoproliferative disease other than successfully and completely resected squamous cell or basal cell skin cancer,
* Any uncontrolled disease: unstable diabetes with documented history of recurrent infections, unstable ischaemic heart disease, moderate to severe heart failure (NYHA stage III/IV), recent stroke and any other disease or condition inducing, in the investigator's opinion, a risk for the patient related to his/her participation in the trial,
* Positive hepatitis B or C serology indicating active infection,
* History of positive HIV serology,
* Persistent infection or severe infections requiring hospitalisation or IV antibiotic therapy during the 30 days prior to inclusion in the trial or oral antibiotic therapy during the 14 days prior to inclusion in the trial,
* History of clinically significant alcohol or other substance abuse during the previous year,
* Previous diagnosis or signs of demyelinating disease of the central nervous system,
* History of active tuberculosis, histoplasmosis or listeriosis,
* Signs of latent tuberculosis (based on a history of nontreated contamination, or an opacity greater than 1 cm on chest x-ray, or a positive intradermal reaction to 5 IU of tuberculin ≥ 5 mm).
* Negative urine pregnancy test in girls with childbearing potential
* Chronic rupture of the blood-aqueous barrier with marked flare on the initial examination but not modified by one month of anti-inflammatory therapy.
* Impossibility to monitor flare:
* Children < 4 years
* False flare due to the presence of giant cells on the surface of an artificial lens or in an aphakic child.
* Children presenting complications such as refractory glaucoma or cataract rapidly requiring surgery.
* Phthisis bulbi with hypotonia and atrophy of the ciliary body.
* Any other situation raising problems for maintenance of stable doses of steroids and immunosuppressive drugs during the period between 4 weeks before D0 and the M2 evaluation. Authorized immunosuppressive therapies that must be maintained at stable dose are steroid eye drops, systemic steroid therapy and once weekly oral or subcutaneous MTX at a dose of *3 to *6 mg (without exceeding 25 mg).
* Any ophthalmologic contraindication
* If female and childbearing potential should have an appropriate contraceptive method during all study period and 5 months after last adalimumab dose. Abstinence with no oral contraception can be considered. |
Study Objectives
High-dose chemotherapy with melphalan and autologous hematopoietic stem cell transplantation (HSCT) is considered standard treatment for patients with multiple myeloma. While autologous HSCT may induce remission in patients resistant to standard chemotherapy, and has been shown to lead to long-lasting disease control in a subgroup of patients, the procedure is not curative. Given enough time and in the absence of a competing cause of death, all patients eventually relapse after auto-HSCT.
The only potentially curative approach currently available in the treatment of multiple myeloma (MM) is stem cell trans-plantation from an allogeneic donor. Allogeneic HSCT eradicates residual myeloma cells through T-cell mediated graft-versus-tumor effects. Allogeneic HSCT is, however, associated with significant risk of graft-versus-host disease and its use is therefore limited to younger patients with high risk dis-ease. Malignant plasma cells in multiple myeloma are also sensitive to natural killer cell lysis. Natural killer cells do not cause graft-versus-host disease, which has led to interest in their therapeutic use in patients with multiple myeloma.
We have previously shown that immunomagnetic separation of a highly pure NK cell product from a leukapheresis is possible and that these cells can be expanded up to 100-fold in a GMP-compatible setting. The current study aims to test the tolerability and feasibility of infusions of in vitro expanded haploidentical NK cells for patients after melphalan 200mg/m2 high dose chemotherapy and autologous HSCT in 10 patients. If feasible, the data will provide a basis for further prospective studies.
Intervention / Treatment
OTHER: Treatment with in vitro expanded haploidentical NK cells
| Inclusion Criteria:
* > 18 years, with multiple myeloma and indication for an autologous HSCT
* Available related haploidentical donor
* Written informed consent
Exclusion Criteria:
* Patients scheduled for autologous/allogeneic tandem HSCT |
Study Objectives
The objective of this study is to compare the progression-free survival (PFS) of the drug combination ramucirumab plus docetaxel to placebo plus docetaxel in previously untreated participants with human epidermal growth factor receptor 2 (HER2)-negative, unresectable, locally-recurrent or metastatic breast cancer.
Intervention / Treatment
BIOLOGICAL: ramucirumab (IMC-1121B), DRUG: docetaxel, OTHER: Placebo
| Inclusion Criteria:
* Participant is able to provide signed informed consent
* Participant is female and ≥ 18 years of age or older if required by local laws or regulations
* Participant has histologically or cytologically confirmed adenocarcinoma of the breast that is now metastatic or locally-recurrent and inoperable with curative intent. Every effort should be made to make paraffin-embedded tissue or slides from the diagnostic biopsy or surgical specimen available for confirmation of diagnosis
* Participant has measurable and/or non-measurable disease
* Participants' primary and/or metastatic tumor is human epidermal growth factor receptor 2 (HER2)-negative by fluorescence in-situ hybridization (FISH) or chromogenic in-situ hybridization (CISH) or 0, 1+ overexpression by immunohistochemistry (IHC)
* Participant has not received prior chemotherapy for metastatic or locally-recurrent and inoperable breast cancer
* Participant completed (neo) adjuvant taxane therapy at least 6 months prior to randomization
* Participant completed (neo) adjuvant biologic therapy at least 6 weeks prior to randomization
* Participant completed all prior radiotherapy with curative intent ≥ 3 weeks prior to randomization
* Participant may have received prior hormonal therapy for breast cancer in the (neo) adjuvant and/or the metastatic setting ≥ 2 weeks prior to randomization
* Participant's left ventricular ejection fraction is within normal institutional ranges
* Participant has resolution to grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI-CTCAE v *0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy which must have resolved to grade ≤ 2
* Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Participant is amenable to compliance with protocol schedules and testing
* Participant has adequate hematological functions \[absolute neutrophil count (ANC) ≥ 1500 cells/microliter (mcL), hemoglobin ≥ 9 grams/deciliter (g/dL), and platelets ≥ 100,000 cells/mcL and ≤ 850,000 cells/mcL\]
* Participant has adequate hepatic function \[bilirubin within normal limits (WNL), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ *5 times the upper limit of normal (ULN), or ≤ *0 times the ULN if the transaminase elevation is due to liver metastases, and alkaline phosphatase ≤ *0 times the ULN\]
* Participant has serum creatinine ≤ *5 x ULN. If serum creatinine > *5 x ULN the calculated creatinine clearance should be > 40 milliliters/minute (mL/min)
* Participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA); if urine protein ≥ 2+, a 24-hour urine collection must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study
* Participant must have adequate coagulation function as defined by international normalized ratio (INR) ≤ *5 and a partial thromboplastin time (PTT) ≤ *5 X ULN if not receiving anticoagulation therapy. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin and if on warfarin must have a INR between 2 and 3 and have no active bleeding (defined as within 14 days of randomization) or pathological condition that carries a high risk of bleeding (such as, tumor involving major vessels or known varices)
* Women of childbearing potential must implement adequate contraception in the opinion of the investigator
* Participant has not received prior biologic therapy for metastatic or locally recurrent and inoperable breast cancer
Exclusion Criteria:
* Participant has a concurrent active malignancy other than breast adenocarcinoma, adequately treated non melanomatous skin cancer, or other non-invasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that she has been disease free for > 3 years
* Participant has a known sensitivity to docetaxel or other drugs formulated with polysorbate 80
* Participant has a known sensitivity to agents of similar biologic composition as ramucirumab or other agents that specifically target vascular endothelial growth factor (VEGF)
* Participant has a history of chronic diarrheal disease within 6 months prior to randomization
* Participant has received irradiation to a major bone marrow area as defined as > 25% of bone marrow (such as, pelvic or abdominal radiation) within 30 days prior to randomization
* Participant has participated in clinical trials of experimental agents within 4 weeks prior to randomization
* Participant has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
* Participant has active, high risk bleeding (such as, via gastric ulcers or gastric varices) within 14 days prior to randomization
* Participant has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
* Participant has uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator
* Participant has brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
* Participant has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
* Participant has pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
* Participant is pregnant or lactating |
Study Objectives
A single-institutional cohort to determine the prevalence of new immunohistochemical panel in advanced triple-negative submitted to neoadjuvant chemotherapy and its association with response and survival.
Intervention / Treatment
| Inclusion Criteria:
* Women older than 18 years
* Locally advanced TNBC (T3-4, any Node, M0; any Tumor, N1-3, M0)
* Patients submitted to anthracycline and taxane-based neoadjuvant chemotherapy and then operated between January 2010 and December 2014 at the Brazilian National Cancer Institute.
Exclusion Criteria:
* Patients with metastatic Breast Cancer;
* Other non-epithelial histologies of breast cancer;
* Pure Ductal Carcinoma In Situ diagnoses are not eligible.
* Patients with scarce material for immunohistochemistry;
* Other primary synchronous or anachronistic tumors in the breast or other sites;
* No prior immunotherapeutic, chemotherapeutic or antiandrogenic drugs allowed
* Patients treated with alternative neoadjuvant chemotherapy regimens (not based on anthracycline and taxane) or with only hormone therapy;
* Patients who received chemotherapy or who were operated outside the INCA. |
Study Objectives
This study is to evaluate the efficacy and safety of Sorafenib in combination with Gemcitabine in patients with advanced/unresectable HCC.
Intervention / Treatment
DRUG: Sorafenib and Gemcitabine
| Inclusion Criteria:
* patient at least 18 years of age with written informed consent prior to enrollment into the study.
* histologically or cytologically confirmed advanced unresectable and/or metastasis) HCC
* Child-Pugh class A or B
* Have measurable disease according to RECIST criteria
* life expectancy of at least 12 weeks, ECOG 0-2
* Have adequate bone marrow reserve and liver and renal function at screening
* Practice adequate contraception during study participation
Exclusion Criteria:
* Exclude medical conditions including history of cardiac disease, HIV infection,active infection,brain metastastasis or intracranial metastasis,seizure disorder requiring medication, history of organ allograft,evidence of or history of bleeding diathesis,previous or concurrent cancer with distinct in primary site or histology (with exception of cervical carcinoma in situ and treated basal cell carcinoma
* Excluded therapies and medications, previous and concomitant : prior systemic anticancer chemotherapy or immunotherapy or targeted therapy,hormonal therapy within 2 weeks,local treatment modality within 4 weeks,radiotherapy within 3 weeks,major surgery and unhealed wound within 4 weeks,autologous bone marrow transplant or stem cell rescue within 4 months
* other condition that may interfere with the patient's participation in the study or evaluation of the results |
Study Objectives
Irreversible electroporation (IRE) is a new, minimal-invasive image-guided treatment method for tumors not amenable for surgical resection or thermal ablation, due to vicinity near vital structures such as vessels and bile ducts. With IRE, multiple electrical pulses are applied to tumorous tissue. These pulses alter the existing transmembrane potential of the cell membranes, and create 'nanopores', after which the cell dies through loss of homeostasis.
The purpose of this study is to investigate the safety of percutaneous IRE in the treatment of patients with locally advanced pancreatic carcinoma (LAPC). Other objectives are feasibility and efficacy of IRE based upon symptomatic response and tumor response.
Fourty patients with histologically confirmed locally advanced pancreatic adenocarcinoma (\<5cm) will undergo percutaneous irreversible electroporation of the tumor using CT and ultrasound guidance. After IRE, patients will be carefully monitored and any (serious) adverse events are registered. Follow-up will consist of frequent CT scanning, as well as serum CA19.9 tumor marker.
We hypothesize that IRE in the pancreas will induce good symptom palliation and local tumor control, without causing severe complications.
Intervention / Treatment
DEVICE: NanoKnife "Irreversible electroporation (IRE)"
| Inclusion Criteria:
Screening must be performed no longer than 2 weeks prior to study inclusion.
* Radiologic confirmation of LAPC by at least ceCT of chest and abdomen (with the upper abdomen scanned according to a dedicated 3mm slice multiphase pancreatic tumor protocol), performed maximum 2 weeks prior to the procedure;
* Maximum tumor diameter ≤ 5 cm;
* Histological or cytological confirmation of pancreatic adenocarcinoma;
* Age ≥ 18 years;
* ASA-classification 0 - 3
* Life expectancy of at least 12 weeks;
* Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to definite inclusion;
* Hemoglobin ≥ *6 mmol/L;
* Absolute neutrophil count (ANC) ≥ 1,500/mm3;
* Platelet count ≥ 100\*109/l;
* Total bilirubin ≤ *5 times the upper limit of normal (ULN);
* ALT and AST ≤ *5 x ULN;
* Serum creatinine ≤ *5 x ULN or a calculated creatinine clearance ≥ 50 ml/min;
* Prothrombin time or INR < *5 x ULN;
* Activated partial thromboplastin time < *25 x ULN (therapeutic anticoagulation therapy is allowed if this treatment can be interrupted as judged by the treating physician);
* Written informed consent;
Exclusion Criteria:
* Resectable pancreatic adenocarcinoma as discussed by our multidisciplinary hepatobiliary team;
* Extrapancreatic metastases;
* Successful down staging after (radio)chemotherapy from previous unresectable/borderline tumor to resectable tumor;
* Stage IV pancreatic carcinoma;
* History of epilepsy;
* History of cardiac disease:
* Congestive heart failure >NYHA class 2;
* Active Coronary Artery Disease (defined as myocardial infarction within 6 months prior to screening);
* Cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker (beta blockers for antihypertensive regimen are permitted);
* Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen;
* Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use of anticoagulants, ascites);
* Uncontrolled infections (> grade 2 NCI-CTC version *0);
* Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment;
* Immunotherapy ≤ 6 weeks prior to the procedure;
* Chemotherapy ≤ 6 weeks prior to the procedure;
* Radiotherapy ≤ 6 weeks prior to the procedure;
* Concomitant use of anti-convulsive and anti-arrhythmic drugs (other than beta blockers used for antihypertensive);
* Allergy to contrast media;
* Any implanted stimulation device;
* Any implanted metal stent/device within the area of ablation that cannot be removed;
* Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study;
Of note, patients with contra-indications for MRI will not be excluded from participation: in this case radiologic follow-up will consist of CT-scanning according to protocol. |
Study Objectives
Chronic Pain, especially neuropathic pain, are adverse events after posterolateral thoracotomy for lung resection. The continuous application of ketamine may have a prophylactic effect and helps to prevent chronic pain. The investigators record the incidence and severity of acute pain and neuropathic pain during a seven day period after thoracotomy as well as the incidence of chronic pain and neuropathic pain after one and three month period. Parallel Group design, comparing one Group with a continuous application (24 hours) of ketamine against a Placebo Group.
Intervention / Treatment
DRUG: Placebo, DRUG: Ketamine
| Inclusion Criteria:
* posterolateral thoracotomy for lung parenchyma resection
* informed consent
* ASA (American Society of Anesthesiologists) Status I-III
Exclusion Criteria:
* history of chronic pain
* history of neuropathic pain
* pregnancy or breastfeeding
* participation in another trial
* hypersensitivity for ketamine
* medication with can influence neuropathic pain (gabapentin, clonazepam)
* history of neurological or behavioral illness
* history of alcohol abuse
* history of chemotherapy or radiation
* opioid medication |
Study Objectives
Myelodysplastic Syndrome (MDS) is a disease of the bone marrow characterized by anemia,neutropenia, and thrombocytopenia (low red blood cell, white blood cell, and platelet counts). MDS patients with thrombocytopenia who fail standard therapies require regular platelet transfusions which are expensive and inconvenient, and are a risk for further serious bleeding complications. The new treatment of MDS using azacitidine has shown to increase the survival rate of MDS patients including to improve platelet production over time. However,in the early cycles of treatment with azacitidine,the low platelet counts tend to exacerbate before they provide any clinical benefit.
Eltrombopag is a drug designed to activate the thrombopoietin receptor. Eltrombopag has been able to increase platelet counts in healthy Thrombocytopenia Purpura (ITP), a disease where patients destroy their own platelets very rapidly and thus develop thrombocytopenia.
Eltrombopag is administered orally and is Therapeutic Goods Administration (TGA) approved for the treatment of thrombocytopenia in patients with chronic ITP who failed to respond to standard treatment.
This study is a single arm pilot study to evaluate the safety and tolerability of Eltrombopag in the treatment of low platelet counts in adult subjects with MDS treated using azacitidine This study also incorporates a correlative laboratory component designed to determined the mechanism of action of 5-azacitidine +/- Eltrombopag and to determine a baseline profile which may predict those most responsive. These studies will incorporate gene methylation and expression, and immunoprofiling.
Intervention / Treatment
DRUG: Azacitidine and eltrombopag
| Inclusion Criteria:
* Patients with low platelet count (<=150 x109/L)and in addition disease diagnosis of either MDS, or nonproliferative CMML or low marrow blast count AML not suitable for induction chemotherapy
* Age >18 years
* ECOG score 0-2 at screening
* Life expectancy ≥12 weeks
* Ability to comply with the adequate contraception in patients of childbearing potential.
Exclusion Criteria:
* Subjects with the diagnosis acute promyelocytic leukaemia
* Prior treatment with azacitidine or any other methyl-transferase inhibitor (e.g. decitabine)
* Prior treatment with eltrombopag, romiplostim, or other TPO-receptor agonist
* AML or MDS requiring cytoreductive therapy (eg hydroxyurea, ara-c, thioguanine etc) in the month prior to study entry
* Known uncontrolled medical conditions which may compromise participation in this study including but not limited to:
* Poorly controlled congestive heart failure: ejection fraction <30% measured in past 6 months) or NYHA class IV
* Arrhythmia known to increase the risk of thromboembolic events.
* Unstable angina or an ischaemic cardiac event requiring hospital admission in the previous 12 months.
* Unresolved GI disease that may significantly alter the absorption of eltrombopag
* Known pro-thrombotic condition as defined by a history ≥1 unprovoked deep venous thrombosis or pulmonary embolism, or any DVT/PE with a procoagulant condition screen suggesting the presence of a procoagulant condition (prothrombin gene mutation homozygosity, factor V leiden homozygosity, antithrombin deficiency, lupus anticoagulant syndrome).
* History of Ischaemic neurological event (TIA or stroke) within the preceding 2 years.
* Inadequate renal function (eGFR <30 ml/min by Cockcroft-Gault (C-G) formula, or as measured by 24 hour urinary creatinine clearance)
* Inadequate hepatic function:
* bilirubin ≥*5xULN - ≤80µmol/L acceptable if attributed to haemolysis, ineffective erythropoiesis or iron overload). This applies also for patients with Gilbert's Syndrome.
* AST or ALT ≥2xULN (≤3xULN acceptable if attributed to transfusion-associated iron overload)
* Patients with known liver cirrhosis.
* Other concurrent severe and/or uncontrolled medical conditions including a history of malignancy other than MDS/AML in the preceding 2 years requiring chemotherapy and/or radiotherapy. Non melanotic skin cancers requiring low dose local radiotherapy or topical agents are allowed on study if considered clinically stable or healed.
* Women who are pregnant or breast-feeding.
* Treatment with growth factors such as erythropoietin, GCSF or stem cell factor in the 21 days prior to commencement of study therapy.
* Active or uncontrolled infections.
* Subjects with known HIV infection.
* Has any other clinically important abnormalities as determined by the investigator that may interfere with his or her participation in or compliance with the study
* Bone marrow fibrosis that leads to an inability to aspirate marrow for quality cytological assessment, termed a "dry tap".
* Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
* Splenomegaly >14cm on the screening ultrasound examination. |
Study Objectives
The purpose of this study is to determine whether adding low dose methotrexate to anti -TNF therapy is more effective than treatment with anti-TNF therapy alone in inducing and maintaining steroid-free remission for children with Crohn's Disease.
Intervention / Treatment
DRUG: Methotrexate, OTHER: Sugar pill (placebo)
| Inclusion Criteria:
* Pediatric Crohn's Disease (PCD) patients, < 21 years of age, ≥20 kg, initiating anti-TNF therapy with infliximab or adalimumab (including biosimilars).
* Diagnosis of Crohn's Disease (CD) established confirmed by the treating clinician, and established by standard clinical criteria (radiography, endoscopy, histology).
* Ability to provide parental permission and child assent (where applicable), or adult consent for patients ages 18-*
Exclusion Criteria:
* Prior use of anti-TNF or other biological therapy for CD
* Lack of stable home address that study medications can be mailed to
* Anticipated short length of follow up at study center (plans for family to move, transition to adult GI (gastrointestinal) provider, etc.). Patients expected to leave practice < 12 months from enrollment should not be enrolled.
* Concurrent pelvic or abdominal abscess. A recent history of abdominal or pelvic abscess, which is controlled, does not exclude the subject.
* Prior intra-abdominal surgery without a clinically significant relapse (i.e. patients starting on anti-TNF for post-op prophylaxis or for endoscopic recurrence only should not be included)
* Receipt of a live virus vaccine within the last 30 days
* Pregnancy, planning to become pregnant, or high risk of pregnancy as determined by the local investigator
* Breastfeeding
* Refusal to stay abstinent or utilize 2 forms of birth control while on study medication (for female patients)
* BMI > 98% for gender and age
* Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years). A recent history of basal cell or squamous cell carcinoma, which is considered surgically cured, does not exclude the subject.Those with a recent history of colonic adenoma or dysplastic lesions should be excluded.
* Known high alcohol consumption (more than seven drinks per week)
* Patients with serum albumin < *5 g/dl
* Patients with white blood cell count (WBC) < *0 x109th/L
* Patients with platelet count < 100 x109th/L
* Patients with initial elevation of liver enzymes (AST or ALT) > *5 times above normal limit
* Patients with known active infection with Clostridium difficile (C. difficile) (untreated infection based on clinician assessment does not apply to colonization or infection controlled with current or prior treatment.)
* Patients with pre-existing hepatic disease
* Patients with pre-existing renal dysfunction (creatinine > *8 for children age<10, creatinine > *2 mg/dl for children age 10-18, and creatinine > *5 mg/dl for adults age 18 years and older).
* Patients with a pre-existing chronic lung disease other than well controlled asthma
* Current treatment with one of the following drugs: Probenecid (Probalan), Acitretin (Soriatane), Streptozocin (Zanosar), Azathioprine (Imuran, Azasan), 6-mercaptopurine (Purinethol, Purixan)
* Other concerns about the patient/family's ability to participate in the study |
Study Objectives
This is a 2 part study for patients with solid tumours. The purpose of Part A is to measure the amount of olaparib or its breakdown products in the bloodstream for up to 72 hours after eating 3 different breakfasts (high calorie, regular and none). In Part B Patients can take olaparib capsules daily and study assessments will be recorded for 6 months (minimum). Treatment can continue for as long as the patient is benefitting. Throughout the study patients will be monitored for any side effects.
Intervention / Treatment
DRUG: Olaparib, OTHER: Dietary Fasted, OTHER: Dietary standard, OTHER: Dietary High Fat
| Inclusion Criteria:
* Patients aged ≥18 years, male and female
* Able to eat a high-fat breakfast within a 30-minute period, as provided by the study site
* Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy and for which no suitable effective standard therapy exists
* ECOG performance status ≤2
* Normal organ and bone marrow function measured within 28 days prior to administration of IP as defined in protocol
Exclusion Criteria:
* Participation in another clinical study with an IP during the last 14 days (or a longer period depending on the defined characteristics of the agents used)
* Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment (or a longer period depending on the defined characteristics of the agents used).
* Toxicities (≥CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia
* Patients unable to fast for up to 14 hours or who have type I or type II diabetes
* Patients who have gastric, gastro-oesophageal or oesophageal cancer |
Study Objectives
The aim of this study is to evaluate Endocuff- assisted colonoscopy in terms of its possible additive contribution in the detection of important lesions, namely polyps and cancers, compared to standard colonoscopy, in a series of patients undergoing back-to-back screening or surveillance colonoscopies in a randomized fashion. Moreover, we aim to assess possible changes regarding post-polypectomy surveillance programs following Endocuff utilization.
Intervention / Treatment
PROCEDURE: standard colonoscopy, PROCEDURE: Endocuff-assisted colonoscopy
| Inclusion Criteria:
* adults undergoing elective screening or surveillance colonoscopy
* symptomatic adults with indication for colonoscopy
Exclusion Criteria:
* age<18 and > 80 years
* poor overall health (ASA III, IV)
* recent abdominal surgery
* presence of abdominal wall hernias
* active colitis
* previous bowel resection
* inflammatory bowel disease
* polyposis syndromes |
Study Objectives
This is a prospective, randomized study of two types of continent ileal neobladder construction in patients undergoing cystectomy for primary bladder cancer. Patients will be randomly assigned to have either a T-pouch or a Studer pouch constructed at the time of their surgery. They will be followed long-term to determine the relative advantages and disadvantages of the two types of diversion. The investigators' hypothesis is that the inclusion of an antireflux mechanism in the T-pouch will result in significantly fewer episodes of symptomatic urinary tract infection, and will have a lower incidence of upper tract dilation and loss of renal function over the long term.
Intervention / Treatment
PROCEDURE: Studer Pouch orthotopic urinary diversion, PROCEDURE: T-Pouch orthotopic urinary diversion
| Inclusion Criteria:
* All patients undergoing radical cystectomy for bladder cancer who are considered candidates for a neobladder reconstruction are eligible for enrollment.
* Diagnosed with primary bladder cancer (any histology).
* Scheduled to undergo a radical cystectomy (cystoprostatectomy in men and anterior exenteration in women).
* Felt by the treating physician to be a candidate for an orthotopic neobladder urinary diversion.
* Be competent and willing to sign the informed consent.
* Patients may have received previous radiation therapy or intravesical or systemic chemotherapy. Patients with documented metastatic disease are not excluded as long as they are felt to be candidates for a continent neobladder urinary diversion.
Exclusion Criteria:
* Patients undergoing radical cystectomy for any malignancy other than primary bladder cancer (for example prostate cancer or colon cancer invading the bladder,or a gynecologic malignancy), or non-malignant disease (such as a neurogenic bladder or radiation cystitis).
* Unwilling or unable to sign the informed consent.
* Not eligible for an orthotopic neobladder reconstruction.
* A history of other malignancy (except for stage I cancer treated with curative intent without evidence of recurrence, clinically localized prostate cancer either untreated or treated with prostatectomy or radiation therapy or hormone therapy,or non-melanoma skin cancer) within the previous 5 years. |
Study Objectives
Phase II trial to study the effectiveness of irofulven in treating patients who have recurrent or persistent ovarian epithelial cancer or primary peritoneal cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
Intervention / Treatment
DRUG: irofulven
| Inclusion Criteria:
* Histologically confirmed ovarian epithelial or primary peritoneal carcinoma
* Recurrent or persistent disease
* At least 1 unidimensionally measurable target lesion\* defined as:
* At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
* Must have received 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin, or another organoplatinum compound for primary disease
* Initial treatment may have included high-dose, consolidation, or extended therapy administered after surgical or non-surgical assessment
* Patients who have not received prior paclitaxel may receive a second regimen containing paclitaxel
* Ineligible for a higher priority GOG protocol (e.g., any active phase III GOG protocol for the same patient population)
* Platinum-sensitive disease
* Platinum-free interval\*\* of more than 6 months, but less than 12 months duration, with no clinical evidence of progressive disease after response to platinum
* Performance status - GOG 0-2 for patients who received 1 prior therapy regimen
* Performance status - GOG 0-1 for patients who received 2 prior therapy regimens
* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Bilirubin no greater than *5 times upper limit of normal (ULN)
* SGOT no greater than *5 times ULN
* Alkaline phosphatase no greater than *5 times ULN
* Creatinine normal
* Creatinine clearance at least 60 mL/min
* No prior congestive heart failure requiring medication
* No uncontrolled hypertension within the past 6 months
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other invasive malignancies within the past 5 years except nonmelanoma skin cancer
* No history of retinopathy and/or macular degeneration
* No neuropathy (sensory and motor) greater than grade 1
* No active infection requiring antibiotics
* No other illness or condition that would preclude study entry
* No prior bone marrow or stem cell transplantation
* At least 3 weeks since prior biologic therapy or immunotherapy for malignant tumor
* One prior non-cytotoxic regimen (e.g., monoclonal antibodies, cytokines, or small-molecule signal transduction inhibitors) allowed
* See Disease Characteristics
* At least 3 weeks since prior chemotherapy and recovered
* No prior irofulven
* No additional prior cytotoxic chemotherapy for recurrent or persistent disease, including retreatment with initial chemotherapy regimens
* At least 1 week since prior hormonal therapy for malignant tumor
* Concurrent hormone replacement therapy allowed
* See Disease Characteristics
* At least 3 weeks since prior radiotherapy and recovered
* No prior radiotherapy to more than 25% of marrow-bearing areas
* Recovered from recent prior surgery
* At least 3 weeks since any other prior therapy for malignant tumor
* No prior anticancer treatment that would preclude study therapy
* One prior noncytotoxic cytostatic regimen for recurrent or persistent disease allowed |
Study Objectives
Patients with myeloproliferative neoplasms Philadelphia chromosome negative (MPNsPh1-) such as Essential thrombocytosis (ET), Polycythemia vera (PV) and Primary Myelofibrosis (PMF) have a higher risk of arterial or deep-vein thrombosis. This is responsible for a significant increase in mortality (up to 31% of increase in thrombosis risk in ET). Cellular inflation and blood hyperviscosity, resulting from these diseases, fail to account for these thromboses, as more than 50% of thrombotic complications happen under adapted antineoplastic drug treatment.
These last years, cellular microparticles (MPs) have been shown to play a major role in thrombogenesis. MPs are generated by apoptosis or the activation of malignant cells, platelets, endothelial cells or monocytes. They are fragments of plasma membrane, smaller than 1 µm, rich in phosphatidylserine, which can express the tissue factor and serve as support for the coagulation factors. Increase in the plasma concentration of procoagulant platelet microparticles has been demonstrated in other thrombotic diseases (acute coronary syndrome, disseminated intravascular coagulation DIC, etc.). The working hypothesis is that platelet microparticles are involved in the hypercoagulability of MPNs patients.
Intervention / Treatment
OTHER: Blood sampling
| Inclusion Criteria for MNPs patients:
* Age > 18
* Establish MNPs Phi- diagnosis (ET, PV, MFP)
* Consent to participate
Inclusion Criteria for healthy volunteers:
* Healthy volunteers matched in age, sex with the MNPs patients, with a normal complete blood and platelet count
* No personal thromboembolic history
* No known thromboembolic risk factor : thrombophilia, cancers, and other disease associated with a thrombotic risk (Atrial fibrillation, etc.)
* Not pregnant
* Non smoker
* For women, no hormonal contraceptives
Exclusion Criteria for MNPs patients:
* Pregnancy
* Patient unable to give consent |
Study Objectives
This is a retrospective real-world study to evaluate the efficacy and feasibility of modified reduce-volume target IMRT in the treatment of patients with non-metastatic NPC
Intervention / Treatment
RADIATION: modified reduce-volume target IMRT
| Inclusion Criteria:
* Pathologic diagnosis (pathologically confirmed by nasopharyngeal biopsy) was nasopharyngeal carcinoma;
* Newly diagnosed, non-metastatic and treated with modified reduce-volume IMRT;
* Patients with baseline MRI date of nasopharynx and neck, and completed the first course of treatment in our hospital;
* Diagnosis time: November 1, 2014 to December 31 , 2017
Exclusion Criteria:
* Disease progression during IMRT;
* Previous malignancy or other concomitant malignant diseases;
* The evaluation information of tumor efficacy can not be obtained;
* Receive blind treatment in other clinical research. |
Study Objectives
The purpose of this study is to assess the efficacy and safety of irofulven-based regimens compared to mitoxantrone plus prednisone in patients with hormone-refractory prostate cancer (HRPC) whose disease has progressed following Taxotere based regimens.
Intervention / Treatment
DRUG: Irofulven, DRUG: Prednisone, DRUG: Mitoxantrone, DRUG: Capecitabine, DRUG: Irofulven
| Inclusion Criteria:
To be included in the study, patients must meet the following criteria:
* Cancer of the prostate confirmed by a biopsy sample.
* 18 years of age or older.
* Disease must have spread beyond the prostate as proven by chest x ray, abdominal and pelvic computed tomography (CT) scan, bone scan or clinical examination.
* At least one prior hormonal treatment with documented disease progression during hormone therapy.
* One previous line of chemotherapy that included Taxotere® (as monotherapy or in combination). This could be in addition to estramustine single agent therapy.
* Disease progression during prior Taxotere-based therapy or within 3 months of discontinuing.
* Recovered from any toxic effects of prior chemotherapy, radiotherapy and surgery.
* Recovered from any toxic effects associated with other investigational drugs, if applicable.
* Signed informed consent obtained prior to initiation of any study-specific procedures or treatment.
Exclusion Criteria:
Patients cannot participate in the study if any of the following apply:
* Unable to use prednisone.
* Prior treatment with irofulven, capecitabine (Xeloda), continuous/protracted infusion 5-FU (5-fluorouracil) (infusion duration greater than or equal to 24 hours), other fluoropyrimidines or mitoxantrone.
* Ongoing treatment with a corticosteroid at a prednisone-equivalent dose > 10 mg/day.
* More than 1 prior treatment with either 153Sm or 89Sr, or radioisotope treatment within 8 weeks prior to entering this study.
* Initiation of treatment with bisphosphonate agents (e.g., pamidronate, etidronate) within 2 months of entering the study. Pre-existing treatment with bisphosphonate agents is to be continued during this study.
* Treatment with warfarin and/or phenytoin within 14 days before entering this study or during the study period.
Please note: There are additional inclusion/exclusion criteria. The study center will determine if patients meet all of the criteria. If patients do not qualify for the trial, study personnel will explain the reasons. If patients do qualify, study personnel will explain the trial in detail and answer any questions. Patients can then decide if they wish to participate. |
Study Objectives
No doubt that children facing surgical procedures are subjected to perioperative distressing, anxious and worrying periods. Several factors included; parental deprivation, anxiety, previously mismanaged experience and anticipating pain from the procedure itself weather diagnostic or curative. Anaesthetic goals should focus at alleviating these unfavorable events that may exacerbate the inevitable associated neurohormal stress response with its injurious effects on the course of the procedure. Moreover, it likely to extend beyond the surgical procedure predisposing these vulnerable group of patients to psychological trauma and chronic behavioral changes.
Bone marrow aspiration (BMA) is a frequent procedure that necessitate a meticulous anaesthetic plane that entails rapid non-traumatic induction together with adequate pain free maintenance and instant smooth recovery after a short time practice. Total intravenous anaesthesia (TIVA) had emerged as alternative anaesthetic technique to inhalational anaesthesia for conscious sedation in BMA cited by many authors.
Propofol a popular anaesthetic/ sedative with a rapid onset, short duration and smooth recovery of consciousness and psychomotor functions with no cumulation. However it is poorly analgesic, depresses respiration and there is a possibility of loss of muscle tone leading to airway obstruction .
Dexmedetomidine is a greatly active α2 adrenergic agonist with a valuable anaesthetic- analgesic saving effects. It augments sedation, hypnosis and preservation of muscle tone with negligible respiratory depression and hemodynamic derangements.
The purpose of the current study is to compare between effects of TIVA using propofol or dexmedetomedine versus sevoflurane for maintenance of anaesthesia in children undergoing bone marrow aspiration.
Intervention / Treatment
DRUG: Sevoflurane, DRUG: Propofol infusion for maintance, DRUG: Dexmedetomidine
| Inclusion Criteria:
* patients aged 3-12 years.
* both sexes
* ASA physical status I and II
Exclusion Criteria:
* Patients with identified allergy to the study medications
* with recognized lipid or carbohydrate deranged metabolism
* cardiac dysrhythmias
* congenital heart diseases
* cardiomyopathy
* significant organ dysfunction. |
Study Objectives
The purpose of this study is to find out what effects, good and/or bad, intermittent dosing of the drug Selumetinib will have on subjects with uveal melanoma. Selumetinib is a drug that blocks (or turns off) methyl ethyl ketone (MEK), a protein activated in some uveal melanoma cells. Selumetinib is a MEK inhibitor. Blocking MEK may stop the cancer from growing.
Intervention / Treatment
DRUG: Selumetinib, 100mg, DRUG: Selumetinib, 125mg, DRUG: Selumetinib, 150mg, DRUG: Selumetinib, 175mg, DRUG: Selumetinib, 200mg, DRUG: Selumetinib, 225mg
| Inclusion Criteria:
* Histopathologically confirmed diagnosis of metastatic or unresectable uveal melanoma. Note - Documentation of mutation status for uveal melanoma will not be required prospectively given the high rate of GNAQ/11 mutations (>90%) in this population
* Able to provide informed consent prior to initiation of study
* Age ≥ 18 years old
* Measurable indicator lesion by RECIST v*1
* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.
* Karnofsky Performance Status ≥ 60% or Eastern Cooperative Oncology Group (ECOG) ≤2
* Ability to take oral medications
* All clinically significant toxicities from prior therapy must be ≤ grade 1 (with the exception of alopecia)
* Organ and marrow function and laboratory values as follows:
* Adequate marrow function
* absolute neutrophil count (ANC) >1500 cells/mm3
* platelet count >100,000/mm3
* hemoglobin >*0g/dL
* Adequate hepatic function
* Angiotensin Sensitivity Test/alternative (AST/ALT)<*5x upper limit of normal if no documented liver disease or <5x upper limit of normal if documented liver disease
* Total bilirubin <*5X upper limit of normal unless known diagnosis of Gilbert's disease
* Alkaline phosphatase <*5x upper limit of normal if no documented liver disease or <6x upper limit of normal if documented liver or bone disease
* Creatinine clearance ≥60 mL/min/*73 m2 for patients with creatinine levels above institutional normal.
* Negative pregnancy test (serum or urine) for women of child bearing potential
* The effects of selumetinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 weeks after study discontinuation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of selumetinib administration.
Exclusion Criteria:
* Patients who have had chemotherapy or immunotherapy within 4 weeks or radiation therapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
* Patients who are receiving any other investigational agents concurrently. Palliative radiation therapy will be allowed as long as the patient meets all other eligibility criteria.
* Have had recent major surgery within a minimum 4 weeks prior to starting study treatment, with the exception of surgical placement for vascular access.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib
* Every effort must be made to avoid the use of a concomitant medication that can prolong the corrected QT (QTc) interval while receiving selumetinib (hyd-sulfate AZD6244). If the patient cannot discontinue medications that prolong QTc interval while receiving selumetinib, close cardiac monitoring should be performed.
* Patients with QTc interval >450 msecs or other factors that increase the risk of QTc prolongation or arrhythmic events (ex. Heart failure, hypokalemia, family history of long QT syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions (see Appendix A) are excluded.
* Prior or current cardiomyopathy including but not limited to the following: known hypertrophic cardiomyopathy, known arrhythmogenic right ventricular cardiomyopathy, previous moderate or severe impairment of left ventricular systolic function (LVEF <45% on echocardiography or equivalent on MuGA) even if full recovery has occurred.
* Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest
* Baseline Left ventricular ejection fraction (LVEF) below the LLN or <55% measured by echocardiography or institution's lower limit of normal (LLN) for MUGA
* Severe valvular heart disease
* Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy
* Acute coronary syndrome within 6 months prior to starting treatment
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because selumetinib may be teratogenic or have abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with selumetinib, breastfeeding should be discontinued if the mother is treated with selumetinib.
* HIV positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with selumetinib.
* Prior treatment with a MEK, Ras or Raf inhibitor
* History of current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) in the eye unaffected by uveal melanoma; intraocular pressure (IOP) >21mmgHG or uncontrolled glaucoma
* History of interstitial lung disease or pneumonitis
* Patients with known Hepatitis B or C
* Refractory nausea and vomiting, active gastrointestinal disease (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
* Patients taking vitamin E supplements while on study
* Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, has been treated with surgery and / or radiation, and has been stable for at least 4 weeks prior to the first dose of study medication
* Any unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy, except for alopecia
* Have evidence of any other significant clinical disorder or laboratory finding that, as judged by the investigator, makes it undesirable for the patient to participate in the study.
* Patients being actively treated for a secondary malignancy |
Study Objectives
In this multicenter trial, we will investigate the use of fludarabine plus rituximab, followed by Campath-1H, in previously untreated patients with CLL/SLL. Patients who are elderly, or who are considered unlikely to tolerate this combination therapy well, will receive single agent rituximab followed by Campath-1H.
Intervention / Treatment
DRUG: Rituximab, DRUG: Fludarabine, DRUG: CAMPTH-1H
| Inclusion Criteria:
To be included in this study, you must meet the following criteria:
* Histologically proven B-cell CLL/SLL
* Positive staining for CD20 antigen
* No systemic chemotherapy.
* Measurable or evaluable disease
* Able to perform activities of daily living with minimal assistance
* Age > 18 years
* Life expectancy > 12 weeks
* Adequate liver and kidney function
* Must be accessible for treatment and follow-up
* Must give written informed consent prior to entering this study.
Exclusion Criteria:
You cannot participate in this study if any of the following apply to you:
* Female pregnant or lactating
* Unstabilized active infection on the basis of neutropenia
* History of previous severe opportunistic infections
* Serious underlying medical conditions
* Central nervous system involvement
* History of other neoplasms, either active or treated within five years
Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have. |
Study Objectives
The purpose of the study is to examine the feasibility and safety of twelve weeks oral supplementation of Epigallocatechin-3-gallate (EGCG) in older survivors of cancer
Intervention / Treatment
DRUG: Epigallocatechin-3-Gallate (EGCG) plus Ascorbic Acid (Vitamin C)
| Inclusion Criteria:
* Be age 65 or over.
* Be diagnosed with stage I-III Cancer.
* Have completed curative intent treatment ≤10 years prior to screening. (Patients on endocrine therapies are allowed to enroll.)
* Have a Fried's Frailty Score (FFS) of ≥ *
* Able to provide informed consent, or have consent given by patient-designated health care proxy per institutional policies and University of Rochester Cancer Control guidelines.
Exclusion Criteria: Study subjects must not:
* Have chemotherapy planned for the during of the study.
* Have abnormal liver function tests (ALT, AST and bilirubin ≥3 times institutional upper limit of normal) per most recent available lab test (within 3 months of screening).
* Have uncontrolled or unmanaged liver disease.
* Consume more than 6 cups of green tea per day.
* Have known allergies to caffeine.
* Be diagnosed with a major psychiatric illness requiring hospitalization within the last year.
* Be diagnosed with dementia.
* Cannot provide informed consent due to lack of decision making capacity (as determined by the patient's oncologist) and has no patient-designated health care proxy per institutional policies and University of Rochester Cancer Control URCC guidelines. |
Study Objectives
This is a single-blind randomized clinical trial. Patients undergoing abdominal tumor surgery were recruited to participate in the study. Apart from routine treatment in the surgical intensive care unit, the subjects were randomly divided into two groups: Propofol group (Group P) and Dexmedetomidine group (Group D) and received continuous intravenous infusion of Propofol (infusion dosage range: 0.3 \~ 1.6 mg/kg/h) or Dexmedetomidine (infusion dosage range: 0.1 \~ 0.7 mcg/kg/h) according to their assigned group. Patients' hemodynamic status was monitored using a chest Bioreactance technique, Continuous Non-Invasive Cardiac Output and Hemodynamic Monitor at preset time points (time of recruitment \[0h\], 2, 4, 6, 12h and 24h). Clinical data such as vital signs, hemodynamic parameters, laboratory results, fluid volume and drugs used were also recorded.
Intervention / Treatment
DRUG: Propofol, DRUG: Dexmedetomidine
| Inclusion Criteria:
* non-emergent major abdominal tumor surgery with ICU admission
* the need of sedation during ICU stay
Exclusion Criteria:
* age older than 99 years
* age younger than 20 years
* refractory arrhythmias
* refractory shock status after resuscitation
* new onset of myocardial infarction
* severe heart failure or NYHA 4
* APACHE score > 30 when recruiting
* severe liver cirrhosis or CHILD B or C
* organ transplantation within one year
* pregnancy
* allergic to propofol or dexmedetomidine |
Study Objectives
The purpose of this study is to collect some parameters which may help to provide guidance on how Androgen Deprivation Therapy (ADT) drugs are renewed and physician satisfaction.
Intervention / Treatment
DRUG: triptorelin
| Inclusion Criteria:
* Adult men, ≥18 years old, with recently diagnosed locally advanced or metastatic prostate cancer scheduled to receive androgen deprivation therapy as monotherapy or as concomitant and adjuvant therapy in association with radiation therapy, with a 1 or 3 month GnRH analogue triptorelin formulation
* Expected survival > 12 months.
* Patients having provided written informed consent.
* Patients mentally fit for completing a questionnaire.
Exclusion Criteria:
* Treatment with any investigational drug within the last 3 months before study entry or planning to participate in a study.
* Patients who already have been treated with a GnRH analogue within the last year.
* Patients with hypersensitivity to GnRH, GnRH analogue, triptorelin or its excipients.
* Patients with a contraindication according to SmPC. |
Study Objectives
The overall goal of this educational program was to increase colorectal cancer screening (CRCS) in men and women who attend Federally Qualified Health Centers (FQHC) in Puerto Rico. FQHCs, referred to in Puerto Rico as "Clínicas 330", are ideal settings to implement innovative approaches to increase CRCS because they serve primarily low-income patients who typically have lower rates of screening. The goal of this study, is to develop and evaluate the impact of a clinic level intervention on increasing CRCS among low-income Puerto Rican men and women aged 50-75, who have either never been screened for colorectal cancer, or are under-screened according recommended guidelines. To evaluate the delivery of the CRCS education program we used a group randomized controlled trial that provided data to determine the effectiveness of the CRC intervention program compared with usual practice (no intervention).
Intervention / Treatment
BEHAVIORAL: ¡Salud! Por la Vida
| Inclusion Criteria:
* Female aged 50-75, patient at a participating FQHC.
* Male aged 50-75, patient at a participating FQHC.
Exclusion Criteria:
* Having completed a fecal occult blood test (FOBT) or a fecal immunochemical test (FIT) in the past year.
* Having completed a sigmoidoscopy in the last 5 years.
* Having completed a colonoscopy in the last 10 years.
* Prior history of colorectal cancer. |
Study Objectives
Investigators hypothesized that goal-directed fluid therapy using stroke volume variation will improve postoperative recovery in patients undergoing free flap reconstruction after head and neck cancer resection. Investigators will compare the effect of goal-directed fluid therapy using stroke volume variation on recovery in patients undergoing free flap reconstruction after head and neck cancer resection.
Intervention / Treatment
PROCEDURE: Standard fluid therapy, PROCEDURE: Conservative fluid therapy
| Inclusion Criteria:
* adult patients of age over 20 years scheduled for free flap reconstruction after head and neck cancer resection
Exclusion Criteria:
* valvular heart disease
* congestive heart failure
* liver failure
* renal failure
* pregnant woman
* allergy to hydroxyethyl starch solutions
* coagulation abnormalities |
Study Objectives
The purpose of this research study is to evaluate a new investigational drug to prevent reoccurrence of neuroblastoma that is in remission. This study drug is called DFMO. The objectives of this study will be to monitor for safety and look at efficacy of DFMO.
The safety of the proposed dosing regimen in this trial will be tested by an on-going risk/benefit assessment during the study. A patient benefiting from treatment, not progressing on therapy, and in the absence of any safety issues associated with DFMO may continue on treatment up to 27 cycles with the expectation that there will be an overall clinical benefit.
The procedures involved in this study include Medical history, Physical exam, Vital signs (blood pressure, pulse, temperature), Blood tests, Urine tests, MRI or CT scan of the tumor(s), meta-iodobenzylguanidine (MIBG) scans, and Bone marrow aspirations. All of these tests and procedures are considered standard of care for this population. Drug administration is also part of this protocol, including an investigational new drug called DFMO.
The proposed dosing regimen is an oral dose of DFMO tablets two times a day for each day while on study. There will be 27 cycles. Each cycle will be 28 days in length.
Intervention / Treatment
DRUG: DFMO
| Inclusion Criteria:
* Age: 0-21 years at the time of diagnosis.
* Diagnosis: histologic verification at either the time of original diagnosis or a previous relapse of high risk neuroblastoma.
* Disease Status: Neuroblastoma that is in remission
* First dose of study medication must be greater than 30 days from completion of cytotoxic and antibody therapy and less than 120 days from previous therapy
* A negative serum or urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
* Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrel implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
* Absolute Neutrophil Count (ANC) > 500/μl and platelet count >50,000/μl
* Organ Function Requirements: Subjects must have adequate liver function as defined by:
* Aspartate Aminotransferase (AST) and Alanine transaminase (ALT) <10x upper limit of normal
* Serum bilirubin must be ≤ *0 mg/dl
* Serum creatinine based on age/gender
* Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:
* Lansky score < 60%
* Body Surface Area (BSA) (m2) of <*25
* Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
* Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the effects of prior chemotherapy (hematological and bone marrow suppression effects).
* Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
* Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded. |
Study Objectives
The aim of this study is to evaluate the feasibility of shear-wave elastography for the diagnosis and staging of breast cancer related lymphedema by assessing the skin and subcutaneous tissues of the arm and forearm, which could serve as a reference standard and be more easily applicable in daily life; and to investigate the relationship between the patients' symptoms and elastographic measurements.
Intervention / Treatment
DIAGNOSTIC_TEST: Shear Wave Elastography and B Mode Ultrasonography, DIAGNOSTIC_TEST: Quick Dash Questionnare, DIAGNOSTIC_TEST: The Lymphedema Life Impact Scale, DIAGNOSTIC_TEST: Questioning lymphedema-related symptoms, OTHER: Extremity circumference and volume measurement
| Inclusion Criteria:
For the patient group
* between the ages of 18-75
* diagnosed with breast cancer-associated lymphedema by lymphoscintigraphy
* being stage 0-1-2 lymphedema according to ISL staging For the control group
* between the ages of 18-75
* no history of breast cancer
Exclusion Criteria:
* History of surgery in the assessment area
* History of trauma at the assessment site
* Active infection in the assessment area
* Presence of congenital or acquired malformations at the assessment site
* Primary lymphedema
* those with any medical condition that may cause edema, such as advanced heart or kidney failure |
Study Objectives
The goal of this research study is to learn if palliative care patients or caregivers, and palliative care physicians or nurses can use a computer program designed to provide information about the symptoms and overall health of cancer patients.
Intervention / Treatment
BEHAVIORAL: Questionnaire and Review Session, BEHAVIORAL: Questionnaire and Review Session
| Inclusion Criteria:
* All patient/caregiver participants will be adults 21 years of age or older.
* Participants will be palliative care cancer patients and/or their designated caregivers.
* Participating patients should be receiving palliative care at the MD Anderson Cancer Center as an inpatient or have attended at least one outpatient appointment; participating caregivers should have provided care to their patient during an inpatient stay or have attended at least one outpatient appointment with their patient.
* Physicians and nurses who are experts in palliative care will be eligible for study participation. For this study's purposes, a physician or nurse with a minimum of four years of experience working in a palliative care setting will be considered an expert in palliative care.
Exclusion Criteria:
* Patients or caregivers who are not able to report on symptom status using the electronic measurement system.
* Patient, caregivers, physicians, or nurses who do not agree to sign the study's informed consent documents. |
Study Objectives
Radiomics, the extraction of large amounts of quantitative image features to convert medical images into minable data, is an in-development field that intends to provide accurate risk stratification of oncologic patients. Published prognostic scores only take clinical variables into account. The investigators hypothesize that a combination of CT/MRI features, molecular biology and clinical data can provide an accurate prediction of medical outcome. The long term objective is to build a Decision Support System based on the predictive models established in this study.
Intervention / Treatment
| Inclusion Criteria:
* Histologically proven glioblastoma
* Diagnosed with a biopsy only
* Treated with curative intent
* Required data available (clinical/radiological/radiotherapy structure set)
Exclusion Criteria:
* |
Study Objectives
This is a multicentre, open-label, randomised phase II trial comparing azacitidine monotherapy with combined azacitidine and vorinostat in patients with newly diagnosed, relapsed or refractory acute myeloid leukaemia or high risk myelodysplastic syndromes ineligible for intensive chemotherapy.
Intervention / Treatment
DRUG: Azacitidine, DRUG: Vorinostat
| Inclusion Criteria:
* Adults with AML (except Acute Promyelocytic Leukaemia (APL)) as defined by the World Health Organisation (WHO) Classification or patients with high risk MDS categorised as INT-2 or high risk according to the International Prognostic Scoring System (IPSS) who are deemed ineligible for intensive chemotherapy on the grounds of age or co-morbidities with ONE of the following disease status:- i) Newly diagnosed OR
ii) Relapsed Disease: patients must have achieved a previous morphological CR and show evidence of recurrent disease OR
iii) Refractory Disease: patients who have failed to achieve a morphological CR with previous therapy
* Patients are able to receive treatment as out-patient
* Adequate renal and hepatic function as defined in the Protocol
* Patients have given written informed consent
* ECOG performance status less than or equal to 2
Exclusion Criteria:
* Patients with greater than class III NYHA cardiac impairment
* Blastic transformation of Chronic Myeloid Leukaemia
* Prior allogeneic/autologous haematopoietic stem cell transplant
* Pregnant or lactating women
* Adults of reproductive potential not willing to use appropriate, effective, contraception during the trial and for specified amount of time afterwards
* Patients who have received prior histone deacetylase inhibitor (HDACi) treatment as anti-tumour therapy. (Patients who have received HDACi treatment for other indications e.g valproic acid for epilepsy may enrol after a 30-day washout period)
* Previous anti-tumour therapies, including prior experimental agents or approved anti-tumour small molecules and biologics, within 30 days before the start of protocol treatment. (Patients receiving anti-tumour therapies to control blood counts may enrol into the trial)
* Patients who have received prior treatment with demethylating agents such as 5-azacitidine or decitabine
* Patients with contraindications to receiving azacitidine or vorinostat such as hypersensitivity, patients unable to have a subcutaneous injection or swallow oral capsules
* Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B, or C) hepatitis
* Any co-morbidity that could limit compliance with the trial |
Study Objectives
Cyclooxygenase-2 (COX-2) is frequently over-expressed in primary breast cancer. There is evidence that COX-2 inhibition exerts anti-tumor effects in breast cancer. To further determine the effect of COX-2 inhibition in primary breast cancer, we aimed at studying the changes in breast cancer tissues of patients treated with the selective COX-2 inhibitor celecoxib.
In a single-centre double-blinded phase II study, breast cancer patients were randomised to receive either pre-operative celecoxib (400 mg) or placebo twice daily for two to three weeks. We collected fresh-frozen pre-surgical biopsies (before treatment) and surgical excision specimens (after treatment) to assess the tumor changes by use a cDNA microarray, which allows to study the genome-wide changes at the transcriptional level.
Intervention / Treatment
DRUG: celecoxib, DRUG: Placebo
| Inclusion Criteria:
* Female patients suspected of having invasive breast cancer, >1 cm in diameter, and in whom there is an indication for a core or incision biopsy
* Age <75 years at time of diagnosis
* Patient willing and able to comply with the study prescriptions
* Patient able to give written informed consent before patient registration/randomisation
* Pre- and post-menopausal patients are eligible
* Hormone receptor positive and negative patients are eligible
* A negative pregnancy test in pre-menopausal women
Exclusion Criteria:
* HIV, HBV or HCV positivity
* Known hypersensitivity to NSAIDs
* A history of upper gastro-intestinal bleeding
* Endoscopically proven upper gastro-intestinal ulceration
* Patients using NSAIDs, including salicyclic acid
* Systemic use of corticosteroids
* A history or the presence of any other malignancy excepting adequately treated squamous cell skin cancer or in situ carcinoma of the cervix
* Patients who have been treated with neo-adjuvant chemotherapy or hormone therapy |
Study Objectives
This is a prospective, observational study of 1,000 subjects with known or suspected cancer and 2,000 subjects with no known cancer.
Potential participants will be asked questions to confirm their eligibility by a nurse navigator, study staff member, or physician.
Informed consent will be carried out for eligible subjects in accordance with applicable federal regulations and International Council for Harmonisation (ICH)/Good Clinical Practice (GCP) guidelines.
Subjects will then complete a survey, and study staff will draw 60 mL of blood and measure the height and weight of the subject.
Where available, data from the medical records of the cancer subjects will reviewed and collected. In addition, non-cancer subjects will be requested to allow access to their medical records as an optional portion of their informed consent.
Intervention / Treatment
| Inclusion Criteria:
* Age 50 or greater
* Ability to understand the nature of this study and give written informed consent
CANCER COHORT:
Either of the following:
* Histologic diagnosis of cancer with no prior systemic or definitive therapy (any stage, including, inclusive of is-situ carcinoma)
Or
* Subject with high suspicion of cancer through radiological and/or clinical assessment who are scheduled for resection or biopsy within 6 weeks of study blood collection and have not received prior systemic or definitive therapy.
NON-CANCER COHORT
* No prior history of cancer
Exclusion Criteria:
ALL PATIENTS
* Evidence of active febrile infection prior to blood draw.
* Women who are pregnant or breast-feeding.
* History of an allogeneic bone marrow, stem cell transplant, or solid organ transplant.
* Judgment by the Investigator or study staff of any other reason that would prohibit the inclusion of the subject in the study.
CANCER COHORT
* Subjects newly diagnosed with a hematologic malignancy, primary central nervous system tumor, prostate cancer, or skin cancer (including melanoma).
* History of, or currently receiving, systemic or definitive cancer treatment including curative surgical resection, chemotherapy, radiation therapy, immunotherapy, and hormone therapy.
NON-CANCER COHORT
* None |
Study Objectives
The purpose of this study is to determine whether the rituximab administration with fludarabine and cyclophosphamide results, are better, than the ones obtained with conventional therapy such as CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) and also to determine whether the rituximab administration as maintenance treatment during two years, increase the global clinical responses and the disease free time interval.
Intervention / Treatment
DRUG: Rituximab Fludarabine Cyclophosphamide
| Inclusion Criteria:
* Previously untreated patients with grade I-III follicular lymphoma (grade B- D from the Working Formulation, centrofollicular lymphoma in the REAL classification), without evidence of histological transformation.
* Clinical diagnose by histological and/or immunophenotypical evaluation with positive results for CD 20 Mo Ab (node, bone marrow).
* Ann-Arbor stage II-IV.
* Male and female patients from 18 to 75 years old.
* Lack of related clinically uncontrolled diseases.
* Lack of VIH infection.
* Performance status (ECOG) of 0, 1, *
* Patients who voluntarily gave informed consent for the study participation.
* Life expectancy > 3 months.
Exclusion Criteria:
* Pregnant or breast-feeding women.
* Women of childbearing age who do not accept to use an effective contraceptive method during the treatment and one year post-treatment.
* Immunodeficiency condition and autoimmune diseases.
* Patients with advanced clinically uncontrolled cardiac, hepatic or renal insufficiency, defined by the following criteria: total bilirubin, alkaline phosphatase or transaminases >2 x upper limit of normal, and serum creatinine value >2 x upper limit of normal.
* Patients previously treated with chemotherapy or radiotherapy.
* History of oncologic disease within the last 5 years, apart from non-melanoma cutaneous neoplasia or carcinoma in situ of uterine cervix. |
Study Objectives
This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0980 administered with taxane-based chemotherapy regimens utilized in patients with locally recurrent or metastatic breast cancer.
Intervention / Treatment
DRUG: GDC-0980, DRUG: bevacizumab, DRUG: paclitaxel
| Inclusion Criteria:
* Locally recurrent or metastatic breast cancer, not amenable to resection with curative intent
* For Arm C: Overexpression of HER2
* Eastern Cooperative Oncology Group Performance Status of 0 or 1
* Adequate hematologic and organ function
* Evaluable or measurable disease per RECIST (Response Evaluable Criteria in Solid Tumors)
* Female patients of childbearing potential must use an acceptable method of contraception to prevent pregnancy and to continue its use for the duration of the study
Exclusion Criteria:
* Prior anti-cancer therapy of more than two regimens of systemic cytotoxic chemotherapy for advanced or metastatic breast cancer
* Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, or hormonal therapy) within a specified timeframe of the first dose of study treatment
* History of Type 1 or Type 2 diabetes requiring regular medication
* History of clinically significant cardiac or pulmonary dysfunction
* History of malabsorption syndrome or other condition that would interfere with enteral absorption
* Any condition requiring full-dose anticoagulants
* Leptomeningeal disease as a manifestation of cancer
* Active infection requiring IV antibiotics
* Active autoimmune disease that is not controlled by non-steroidal anti-inflammatory drugs, inhaled steroids, or the equivalent of <= 10 mg/day of prednisone
* Known clinically significant history of liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis
* Known HIV infection
* Known untreated or active CNS metastases
* Pregnancy, lactation, or breastfeeding
* Major surgical procedure, open biopsy, or significant traumatic injury within a within a specified timeframe of the first dose of study treatment
For Arm B:
* Uncontrolled hypertension, complication from hypertension, myocardial infarctions, unstable angina, vascular disease or stroke within a specified timeframe of the first dose of study treatment
* Evidence of bleeding diathesis or significant coagulopathy including hemoptysis within a specified timeframe of the first dose of study treatment
* History of abdominal conditions (e.g., fistula, perforation, obstruction) that would preclude use of bevacizumab
* Serious, non-healing wound, active ulcer, or untreated bone fracture
* Proteinuria |
Study Objectives
This phase II trial studies the best dose and how well liposomal cytarabine-daunorubicin CPX-351 (CPX-351) works in treating patients with newly diagnosed acute myeloid leukemia and who are at risk for not responding well to treatment. Liposomal cytarabine-daunorubicin CPX-351 combines two chemotherapy drugs that are known to help each other work better, and may work to stop the growth of cancer cells by blocking the cells from dividing.
Intervention / Treatment
OTHER: Laboratory Biomarker Analysis, DRUG: Liposome-encapsulated Daunorubicin-Cytarabine
| Inclusion Criteria:
* Ability to understand and voluntarily sign an informed consent form
* Pathological diagnosis of AML according to World Health Organization (WHO) criteria (with at least 20% blasts in the peripheral blood or bone marrow): newly diagnosed de novo AML; except for acute promyelocytic leukemia (APL); newly diagnosed secondary AML, defined as having a history of an antecedent hematologic disorder (myelodysplastic syndromes \[MDS\], myeloproliferative disease \[MPD\] or history of cytotoxic treatment for non-hematologic malignancy) or apparent de novo AML with MDS-associated karyotype
* Eastern Cooperative Oncology Group (ECOG) performance status 0-3
* Serum creatinine =< *0 mg/dL
* Serum total bilirubin =< *0 mg/dL
* Serum alanine aminotransferase < 3 times the upper limit of normal (ULN); Note: If elevated liver enzymes are related to disease alanine aminotransferase (ALT) should be < 5 times ULN
* To be considered at high risk for induction mortality patients must have 1 or 2 of the following risk factors (patients >= 60 must have at least 1 risk factor, patients < 60 must have at least 2 risk factors) present; at least one risk factor in every patient must be an AML-related factor:
* AML-related factors include:
* Antecedent hematologic disorder (AHD) (MDS, chronic myelomonocytic leukemia \[CMML\], or MPD) or history of exposure to cytotoxic chemotherapy \[therapy-related (t)-AML\]), or WHO-defined AML with MDS-related changes or apparent de novo AML with MDS-associated karyotype
* Unfavorable cytogenetics as defined by the European Leukemia Net
* Patient-related factors:
* Age >= 70
* ECOG performance status (PS) >= 2
* Co-morbidities:
* Serum creatinine > *3 g/dL
* Cardiac ejection fraction >= 50% by echocardiography or multi gated acquisition (MUGA) (when left ventricular ejection fraction \[LVEF\] expressed as a range, at least the upper limit should include 50%)
* Able to adhere to the study visit schedule and other protocol requirements
* All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile
Exclusion Criteria:
* Patients with history of second malignancy are eligible if they have documentation of disease stability, off therapy, based on computed tomography (CT) scan or other measures for the 6 months prior to entry in core
* Any serious medical condition or psychiatric illness that would prevent the patient from providing informed consent
* Chemotherapy or other investigational anticancer therapeutic drugs in the two weeks prior to study entry; in the event of rapidly proliferative disease, however, the use of hydroxyurea is permitted up to 24 hours before study entry in core
* Evidence of active central nervous system (CNS) leukemia
* Pregnant or lactating women
* Uncontrolled infection; to be eligible, patients receiving treatment for an infection (antibiotic, antifungal or antiviral treatment) must be afebrile (< *3 degrees Celsius \[C\]) and without hemodynamic instability or dyspnea from pneumonia for > 48 hours (hrs) prior to the start of induction therapy
* Hypersensitivity to cytarabine, daunorubicin or liposomal products
* History of Wilson's disease or other copper-metabolism disorder |
Study Objectives
This study evaluates the use of ABI-1968, a topical cream, in the treatment of cervical precancerous lesions in females without human immunodeficiency virus (HIV) infection.
Intervention / Treatment
DRUG: Topical ABI-1968
| Inclusion Criteria:
* Women, 25 to 50 years old.
* Biopsy-confirmed cervical HSIL that is p16+ within 60 days of enrollment (dosing) with no evidence of invasive cancer in any specimen.
* Colposcopy is satisfactory based on visualization of the entire squamo-columnar junction (SCJ). The borders of all lesions must be completely visible.
* The upper limit of the visible (usually aceto-white) lesion is within 3 quadrants or less at screening.
Exclusion Criteria:
* Women who are pregnant, plan to become pregnant in the next 4 months, or lactating females.
* HIV positive (tested at screening visit or within 3 months of screening visit).
* Resolution of visible CIN lesion prior to enrollment.
* ECC positive for glandular disease (adenocarcinoma in situ) or invasive cancer.
* History of cervical cancer, colposcopy suspicious for cancer, any prior treatment of CIN, or hysterectomy. |
Study Objectives
Currently, publicly funded standard of care testing in Ontario for stage IV lung cancer patients uses individual gene tests to look for mutations in the EGFR and ALK genes. This testing broadens treatment options for patients, however there are other gene mutations with corresponding targeted treatments that are not routinely tested for. This study will evaluate the utility and added value of using a next generation sequencing (NGS) panel, the Oncomine Comprehensive Assay v3, to profile stage IV lung cancer patients.
Intervention / Treatment
DIAGNOSTIC_TEST: Oncomine Comprehensive Assay
| Inclusion Criteria:
* Age ≥ 18 years of age
* Pathologic or cytologic confirmation of lung adenocarcinoma (mixed adenocarcinoma and sarcomatoid features permitted)
* Stage IV disease
* Sufficient FFPE tumour tissue for OCCP testing
* Performance status 0-2
* Candidates for targeted therapy (TKIs) and/or clinical trials as determined by the patient's medical oncologist
* Prognosis > 6 months
* Known translocations of RET, MET exon14 skipping variants, or MET amplification are allowed
Exclusion Criteria:
● Patients with known EGFR, KRAS, BRAF and ERBB2 mutations or ALK or ROS1 fusions at study entry unless acquired resistance to molecularly targeted therapy |
Study Objectives
Actinic keratosis are of utmost medical and economical interest because of their high prevalence (20 % of 60 year-old people and older in the Northern hemisphere) and their important cosmetic impact as such actinic keratosis mostly appear on photo-exposed skin sites. The surgeon in charge of such lesions' removal (i) some actinic keratosis adjoining carcinoma to be resected therefore causing the problem of functional areas damaging (eyelids, lips, etc.) or (ii) numerous actinic keratosis localized away from carcinoma (photo-carcinogenesis field) faces the issue of clinical evaluation of such lesions: which ones will spontaneously regress (it is supposed to be the case for 20 % of such lesions);which ones will remain and which ones will develop into invasive carcinomas ?
A non-invasive, non-traumatic, automated and real-time help for the clinical diagnosis orientation of such skin lesions could help improving diagnosis accuracy of the medical practitioner's visual inspection:
* In terms of sensitivity in order to potentially decrease the number of actinic keratosis evolving towards invasive carcinoma,
* In terms of specificity in order to potentially decrease useless resections and reduce resection margins and therefore reduce scars surface.
Intervention / Treatment
DEVICE: bimodal optical spectroscopy
| Inclusion Criteria:
* Adults, and
* Autonomous: enjoying full citizenship rights and full mental abilities, and
* Affiliated to a social security system, and
* Suffering from carcinomatous or polymorphous skin lesions that can be fully managed in an outpatient (ambulatory) surgery procedure.
Exclusion Criteria:
* Carcinomatous or polymorphous skin lesions that require day admission, or
* Carcinomatous or polymorphous skin lesions for which resection margins are uncertain, or
* Naevomatous skin lesions and related skin pathologies. |
Study Objectives
The purpose of this study is to determine whether very high dosages of chemotherapy will improve the chance of surviving cancer.
Intervention / Treatment
PROCEDURE: Myeloablative Chemotherapy, PROCEDURE: Stem Cell Rescue
| Inclusion Criteria:
* Patients must be ineligible for other IRB-approved myeloablative regimens, be 21 years old or younger, and must have a histologically-confirmed Wilms' tumor, liver cancer, recurrent brain tumor of childhood, nasopharyngeal carcinoma, fibrosarcoma, desmoplastic small round cell tumor, germ cell tumor or other small round cell tumor, which:
* is metastatic and has < 25% cure rate with conventional treatment; or
* progressed after prior chemotherapy and has < 25% salvage rate with non-myeloablative therapies.
* Disease status: Within 3 weeks of initiation of this protocol, patients must:
* be in a complete or good partial remission (section *4); or
* have a "chemosensitive" tumor, which is defined as a > 50% decrease in at least one measurable tumor parameter attributable to prior chemotherapy, without evidence of progressive disease by any other parameter.
* Prior chemotherapy: Before entry to this protocol, patients must have derived maximal benefit from conventional, i.e., nonmyeloablative, doses of combination chemotherapy. Conventional therapy should be continued until either a complete remission is achieved, no further benefit from non-myeloablative dosing can be appreciated, or toxicity from conventional therapy is perceived as limiting in the absence of stem cell rescue. The cancer must be proven to be sensitive to alkylating agents. This means that, in addition to, or as part of, the appropriate chemotherapy protocol for the specific cancer in question, all patients must have received and responded to a minimum of:
* 2 courses of high-dose cyclophosphamide, totaling > 4200 mg/m2; or
* courses of high-dose ifosfamide totaling > 12 gm/m*
* 1 course of "a)" above, plus 1 course of 'b)" above.
* Equivalent high dose alkylating agents as described in *3 a, b, and c.
* Patients must have adequate renal hepatic, and cardiac function (sections *4-*6).
* Patients must meet at least one of the following stem cell requirements (Peripheral blood collection is to be preferred when available as an option):
* Harvested bone marrow must contain 1 x 108 nucleated cells per kg of body weight, or,
* Peripheral blood collection should include at least 2 x 106 CD34+ cells/kg.
* Informed consent must be signed indicating patient and/or parental awareness of the investigational nature of this program |
Study Objectives
In this study, glycosaminoglycan (GAG) profiling in subjects diagnosed with metastatic renal cell carcinoma (mRCC) is hypothesized to be useful in monitoring drug response and predict radiological response. To this end, glycosaminoglycan scores based on longitudinal samples of plasma and urine in prospectively enrolled patients will be correlated to radiological response to first-line therapy based on current standard-of-care. A positive correlation indicates that glycosaminoglycan scores can successfully detect patients that are not responding to treatment before the scheduled follow-up in which radiological imaging is performed. Data on the extent of metastasis (number of metastatic sites) will be collected to assess whether glycosaminoglycans correlate accordingly.
Intervention / Treatment
| Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Diagnosis of renal cell carcinoma
* Metastatic disease
* Predicted life expectancy over 2 months
* Patient referred for first line drug therapy
* Standard imaging evaluation 12 weeks prior to inclusion
* Planned for standard imaging within 16 weeks after start of therapy
* Informed consent
Exclusion Criteria:
* Lack of proper compliance to accept continuous samplings |
Study Objectives
The goal of this clinical research study is to find the highest tolerable dose of carfilzomib that can be given to patients with lymphoma after a stem cell transplant. The safety of this drug will also be studied.
Carfilzomib is designed to block cancer cells from repairing themselves. If the cancer cells cannot repair themselves, this may cause them to die.
Intervention / Treatment
DRUG: Carfilzomib, DRUG: Dexamethasone
| Inclusion Criteria:
* Patients with mantle cell lymphoma, T-cell lymphoma, and diffuse large b-cell lymphoma within 6 months post autologous transplantation and without relapse.
* Age >/= 18 years to </= 70 years.
* Absolute neutrophil count (ANC) >/= to *5 x 10\^9/L; Platelets > 75 x 10\^9/L.
* No active infection.
* Performance status: Eastern Cooperative Oncology Group (ECOG) 2 or less or Karnofsky of at least *
* Cardiac EF >/= 45% by 2D-Echo.
* Serum creatinine less than *6 mg/dl and Creatinine Clearance >/= to 30 mL/min.
* Liver function tests less than 2x upper limit of normal range (unless related to medications or Gilbert's disease).
* Females of childbearing potential who are not pregnant or breastfeeding.
* Patient or legally authorized representative able to sign informed consent.
Exclusion Criteria:
* Glucocorticoid therapy (prednisone >30 mg/day or equivalent within 14 days of first dose.
* POEMS syndrome.
* Plasma cell leukemia or circulating plasma cells >/= 2 X 10\^9/L.
* Waldenstrom's Macroglobulinemia.
* Patients with known amyloidosis.
* Immunotherapy or chemotherapy with approved or investigational anticancer therapeutics within 21 days of first dose.
* Patients previously randomized in any other Onyx-sponsored Phase 3 trial.
* Active congestive heart failure (NYHA Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months.
* Acute active infection requiring systemic antibiotics, antiviral (except antiviral directed at Hepatitis B) or antifungal agents within 14 days of first dose.
* Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B SAg or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed).
* Patients with known cirrhosis.
* Second malignancy within past three years except: a. adequately treated basal or squamous cell skin cancer. b. carcinoma in situ of the cervix. c. prostate cancer < Gleason Score 6 with stable prostatic specific antigen (PSA) over the past three months. d. breast cancer in situ with full surgical resection. e. treated medullary or papillary thyroid cancer.
* Patients with myelodysplastic syndrome.
* Significant neuropathy (Grades 3 to 4, or Grade 2 pain).
* Known hypersensitivity to carfilzomib.
* Known contraindication to dexamethasone.
* Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days of first dose.
* Any other clinically significant medical disease or psychiatric condition that, in the Investigator's opinion, may interfere with protocol compliance. |
Study Objectives
This phase II trial studies the side effects and how well daratumumab works in treating patients with multiple myeloma when the infusion is accelerated. Monoclonal antibodies, such as daratumumab, may interfere with the ability of tumor cells to grow and spread.
Intervention / Treatment
BIOLOGICAL: Daratumumab
| Inclusion Criteria:
* Patients must have received >= 2 daratumumab infusions and be scheduled to receive another dose
* All races and ethnic groups are eligible for this study
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* Any other medical condition, including mental illness or substance abuse, deemed by the principal investigator to likely interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
* Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug
* Prisoner |
Study Objectives
For patients with cerebral oligometastases who are in adequate clinical condition stereotactic radiosurgery (SRS) is the treatment of choice, being recommended by international guidelines for the treatment of one to four lesions. Newer findings have shown that for patients with more than four lesions SRS can be considered as a favorable alternative to whole-brain radiotherapy (WBRT), the currently established standard-of-care treatment. With modern techniques highly conformal SRS of multiple lesions has become feasible with comparable clinical effort and minimal toxicity as compared to WBRT. Developments in magnetic resonance imaging (MRI- imaging) have produced highly sensitive contrast-enhanced three-dimensional fast spin echo sequences such as SPACE that facilitate the detection of very small and early-stage lesions in a fashion superior to the established Magnetization Prepared Rapid Gradient Echo (MPRAGE) series.
Since it has been established that the response of brain metastases to SRS is better for smaller lesions and that WBRT can come at the price of significant neurotoxicity, the investigators hypothesize that 1) earlier detection of small brain metastases and 2) early and aggressive treatment of those by SRS will result in an overall clinical benefit by delaying the failure of repeated localized therapy and thus preserving quality of life and potentially prolonging overall survival. On the other hand however, overtreatment might be a valid concern with this approach since it has yet to be proved that a clinical benefit can be achieved.
The current study aims to stretch the boundaries of the term "cerebral oligometastases" by performing SRS for up to ten cerebral metastases, compared to the established clinical standard of four, given that existing data supports the non-inferiority of this approach and given that modern Cyberknife SRS facilitates the treatment of multiple lesions with minimal treatment-associated toxicity.
Intervention / Treatment
RADIATION: stereotactic radiosurgery (SRS)
| Inclusion Criteria:
* radiologically confirmed metastases of the brain with an underlying history of a malignant illness
* between one and ten suspect intracranial lesions, taking into consideration all available series of the pre-therapeutic MRI (performed at Heidelberg University Hospital and including SPACE sequence)
* age ≥ 18 years of age
* Karnofsky Performance Score (KPS) ≥ 70
* for women with childbearing potential, (and men) adequate contraception.
* ability to understand character and individual consequences of the clinical trial
* written informed consent (must be available before enrolment in the trial)
Exclusion Criteria:
* refusal of the patient to take part in the study
* Small-cell lung cancer (SCLC) as primary malignant illness
* More than 10 suspect intracranial lesions in the initial pre-therapeutic MRI imaging (performed at Heidelberg University Hospital and including SPACE sequence)
* metastasis so close to OAR that initial single-session SRS would be impossible due to lacking radiotolerance
* known contraindications against the performing of cranial MRI
* previous radiotherapy of the brain
* Patients who have not yet recovered from acute toxicities of prior therapies
* Pregnant or lactating women
* Participation in another clinical study or observation period of competing trials, respectively |
Study Objectives
The purpose of this study is to determine if the, MR guided, laser interstitial thermal therapy (LITT) treatment technique can be safety and efficiently used for the human liver metastasis
Intervention / Treatment
DEVICE: MR-guided Laser Interstitial Thermal Therapy System
| Inclusion Criteria:
* Patients 18 years of age or older
* Patients with liver metastasis, originating from colon and liver cancer and proved by histological analysis
* Patient that are scheduled for a surgical resection of part of the liver,
* Patient having a liver metastasis, originating from colon and rectal cancer, smaller or equal to 3 cm
* Patients having the liver metastasis at a distance of at least 1 cm or from the hepatic capsule or/and from a vascular structure
Exclusion Criteria:
* Patients younger than 18 years old
* Patients presenting contra indication for MRI studies
* Patient presenting contra indication to liver surgery
* Patients who already had other interstitial treatment on the targeted lesion |
Study Objectives
Abiraterone is a selective inhibitor of androgen biosynthesis that potently and irreversibly blocks CYP17, a crucial enzyme in testosterone and estrogen synthesis. A pro-drug of abiraterone, abiraterone acetate (Zytiga®), was developed to overcome its poor bio-availability and is fully converted to the active moiety abiraterone. Abiraterone acetate tablets are administered at a fixed oral dose of 1000mg QD in a fasted state in combination with 10mg prednisolon daily.
Abiraterone acetate has a low solubility in aqueous media and a low permeability. The bioavailability of abiraterone acetate is significantly influenced when ingested with food. Ingesting abiraterone acetate with a low fat or a high fat meal resulted respectively in a 5- or 10-fold increase in AUC0-∞. The high and low fat FDA meals used in these food effect studies differ largely from breakfasts taken in everyday life (ca. 800-1000 cal). A continental breakfast contains 160 to 320 calories of which 25-50% is fat, is more compatible with a normal lifestyle and therefore easily sustainable in daily practice. However, the effect of a continental breakfast on the absorption of abiraterone is unknown yet. Furthermore, increasing healthcare costs are a growing concern in all developed countries. Therefore effort should be invested to keep anticancer treatment affordable. A food intervention resulting in a better absorption and enhanced exposure to abiraterone, can lead to a reduced dose, which could significantly impact health care costs for a tumor which is as prevalent as metastatic prostate cancer.
Therefore the investigators want to perform a bioequivalent study to investigate what dose of abiraterone with a continental breakfast equals the dose of 1000mg taken in fasted conditions.
Intervention / Treatment
DRUG: abiraterone
| Inclusion Criteria:
* Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up.
Note: informed consent may be obtained prior to start of the specified screening window.
Note: procedures conducted as part of the subject's routine clinical management (e.g. blood count) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.
* ≥ 18 year old men who use or will start with abiraterone.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-*
* Feasible to collect blood samples from.
Exclusion Criteria:
* Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
* Malabsorption syndrome.
* Major resection of the stomach or small bowel.
* Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
* Unable or unwilling to discontinue use of prohibited medications listed in APPENDIX 3 for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of day 1 and for the duration of the study.
* Concurrent use of other substances known or likely to interfere with the pharmacokinetics of abiraterone. |
Study Objectives
Phase II:
Primary objective: to select one of the 2 test arms (docetaxel with cisplatin, docetaxel with cisplatin and 5-FU), based primarily on complete responses, to advance to a phase III survival comparison against the CDDP + 5-FU control arm.
Secondary objective: to evaluate the quantitative and qualitative safety profile of the 2 test groups.
Phase III:
Primary objective: to detect a statistically significant increase in time to progression (TTP) for the test arm (docetaxel plus cisplatin and 5-FU) relative to the control arm (cisplatin plus 5-FU).
Main secondary objective: to detect a statistically significant increase in overall survival (OS) for the test arm (docetaxel plus cisplatin and 5-FU) relative to the control arm (cisplatin plus 5-FU).
Other secondary objectives: to compare response rates, time to treatment failure, duration of response, safety profiles, quality of life and disease-related symptoms.Socio-economic data will be collected in order to be able to perform an analysis by country when necessary.
Intervention / Treatment
DRUG: XRP6976
| Inclusion Criteria:
* Patient's consent form obtained, signed and dated before beginning specific protocol procedures.
* Gastric adenocarcinoma including adenocarcinoma of the esophagogastric junction, histologically proven.
* Measurable and/or evaluable metastatic disease; if a single metastatic lesion is the only manifestation of the disease, cytology or histology is mandatory. Locally recurrent disease is accepted provided that there is at least one measurable lesion (e.g. lymph node).
* Performance status Karnofsky index > 70%.
* Life expectancy of more than 3 months.
* Adequate haematological and biochemistry parameters
* No prior palliative chemotherapy, previous adjuvant (and/or neo-adjuvant) chemotherapy is allowed if more than 12 months has elapsed between the end of adjuvant (or neo-adjuvant) therapy and first relapse.
Exclusion Criteria:
* Pregnant or lactating women.
* Patients (M/F) with reproductive potential not implementing adequate contraceptive measures.
* Other tumor type than adenocarcinoma (leiomyosarcoma ; lymphoma).
* Any prior palliative chemotherapy. Prior adjuvant (and/or neo-adjuvant) chemotherapy with a first relapse within 12 months from the end of adjuvant (or neo-adjuvant).
* Prior treatment with taxanes. Prior CDDP as adjuvant (and/or neo-adjuvant) chemotherapy with cumulative dose > 300 mg/m². |
Study Objectives
This phase II trial is studying how well giving gossypol together with androgen ablation therapy works in treating patients with newly diagnosed metastatic prostate cancer. Gossypol may stop the growth of tumor cells by blocking blood flow to the tumor. Androgens can cause the growth of prostate tumor cells. Luteinizing hormone-releasing hormone agonists and drugs, such as bicalutamide, may lessen the amount of androgens made by the body. Giving gossypol together with androgen ablation therapy may be an effective treatment for prostate cancer
Intervention / Treatment
DRUG: AT-101, DRUG: Bicalutamide, OTHER: LHRH agent
| Inclusion Criteria
* Histologically proven adenocarcinoma of the prostate with clinical stage D2 disease defined by soft tissue or bony metastasis.
* Patients must have elevated PSA ≥ 5 ng/ml within 12 weeks prior to registration. Androgen ablation therapy, which must include an LHRH agonist, will begin 6 weeks prior to initiation of AT*
* Patients are allowed prior local therapy with radiation or surgery. Patients must not have received more than 12 months of androgen ablation therapy or antiandrogen therapy in the adjuvant/neoadjuvant setting and no prior androgen ablation therapy for metastatic disease, beyond the six week induction period prior to initiation of AT* Patients with prior adjuvant/neoadjuvant androgen ablation therapy must have completed such therapy at least 12 months prior.
* Must be 18 years old or older.
* Life expectancy of greater than 6 months.
* ECOG performance status ≤ *
* Patients must have normal organ and marrow function as defined below:
* leukocytes ≥ 3,000/mcL
* absolute neutrophil count ≥ 1,500/mcL
* platelets ≥ 100,000/mcL
* total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SGPT) ≤ *5 X institutional upper limit of normal
* creatinine within normal institutional limits OR
* creatinine clearance ≥ 60 mL/min/*73 m2 for patients with creatinine levels above institutional normal
* There must be no plans to receive concomitant chemotherapy or radiation therapy during the study period. Baseline and on study PSA values must be obtained from the same reference laboratory.
* The effects of AT101 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason men and/or their partners must agree to use adequate contraception, (including hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation.
Exclusion Criteria
* Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
* Patients may not be receiving any other investigational agents.
* Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to AT101 or other agents used in the study.
* Patients with bilateral orchiectomy are not eligible.
* Patients presenting with acute cord compression are not eligible.
* History of bowel obstruction or GI dismotility disorder.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain AT-101 tablets.
* Requirement for routine use of hematopoietic growth factors (including granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, or interleukin-11) or platelet transfusions to maintain absolute neutrophil counts or platelets counts above the required thresholds for study entry.
* HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AT-* |
Study Objectives
This study will test the effectiveness of an 8-week group intervention for African American men who have been treated for prostate cancer. The group intervention is based on 1) the cognitive-behavioral theoretical approach to improving adjustment to cancer and 2) masculinity theory as it relates to coping strengths and preferences in men. We will test the effectiveness of this coping skills intervention for improving survivors' quality of life in 4 areas: 1) distress related to sexual, urinary, and bowel symptoms; 2) self-confidence for managing symptoms; 3) overall emotional functioning; and 4) overall physical functioning. The effect of the coping skills group intervention in these 4 areas will be compared to a comparison intervention in which African American men will receive basic education about prostate cancer, but will not participate in coping skills training.
Intervention / Treatment
BEHAVIORAL: Coping Skills Training, BEHAVIORAL: Prostate Cancer Education
| Inclusion Criteria:
* Diagnosis of early stage, localized prostate cancer (T1-T3)
* Must have received treatment within previous 2 years
* Capable of self-care per Karnofsky Performance Status score of 60+
* African American
* Must have physician who can confirm treatment history
Exclusion Criteria:
* Undergoing primary treatment 2 or more years ago
* Having regional or metastatic prostate cancer at time of screening |
Study Objectives
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Vaccines made from a person's cancer cells may make the body build an immune response to kill cancer cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Combining chemotherapy with vaccine therapy and peripheral stem cell transplantation may be effective in treating multiple myeloma.
PURPOSE: Phase I/II trial to study the effectiveness of chemotherapy followed by vaccine therapy and peripheral stem cell transplantation in treating patients who have newly diagnosed multiple myeloma.
Intervention / Treatment
BIOLOGICAL: GVAX, PROCEDURE: Autologous transplant
| INCLUSION CRITERIA
Initial Presentation
* Age between 18 and 70 years
* ECOG 0 - 2
* Patients with histologically confirmed multiple myeloma with ≥ 30% bone
* marrow involvement and a de novo presentation. One cycle of prior
* chemotherapy for myeloma is allowed. Local radiation therapy is permitted
* Ability to give informed consent
* No existing secondary malignancies and no history of secondary malignancies in the past 5 years (other than a history of carcinoma in situ of the cervix, superficial skin cancer, or superficial bladder cancer)
* No active autoimmune disease, nor a history of any autoimmune disease requiring medical treatment with systemic immunosuppressants
* No corticosteroids within 28 days of tumor harvest
* No major active medical or psychosocial problems that could be exacerbated or complicated by this treatment
* Not pregnant
* HIV negative
* AST/ALT, total bilirubin < threefold normal
* Absolute neutrophil count >500/mm3
* Platelet count >30,000/mm3
Prior to Transplantation
* ECOG performance status of 0 - *
* No active/uncontrolled infection.
* Absolute neutrophil count (ANC) >1000/mm*
* Platelet count >50,000/mm*
* Hemoglobin >8g/dL
* AST/ALT, total bilirubin <3-fold normal.
* 50% or greater reduction in tumor burden with prior chemotherapy
* Patient has received a minimum of 2 cycles of an accepted induction
* chemotherapy regimen
* Patient fulfills the requirements for standard peripheral stem cell transplantation Prior to Posttransplant Vaccination
* No active/uncontrolled infection
* Absolute neutrophil count (ANC) >1000/mm3
* Platelet count >50,000/mm3
* Hemoglobin >8g/dL
* AST/ALT, total bilirubin <3-fold normal
* No unresolved Grade 3 or 4 adverse events related to the transplant
EXCLUSION CRITERIA
* Failure of autologous tumor-cell processing for vaccine production |
Study Objectives
Colorectal cancer screening by faecal occult blood test (FOBT) is a high public health priority. The interest of guaiac tests (G-FOBT) is limited by their poor sensitivity, while the superiority of I-FOBT in comparison with G-FOBT is now established. Nevertheless automated quantitative I-FOBTs have not been compared, and the optimal number of samples and threshold is not yet fixed. The aim of this study is to compare the performances of the 2 more well-known I-FOBTs with automated analyzers (magstream by Fujirebio, and OC Sensor by Eiken) for different positivity thresholds and numbers of samples in general average risk population. Patients will performed a two samples Magstream, a two samples OC Sensor and Hemoccult II. In case of a positive test, a colonoscopy will be performed. Sensitivity and specificity for detection of cancer and advanced neoplasias will be compared between tests using ratio of sensitivities (RSN) and ratio of false positives (RFP) according to number of samples and positivity threshold.
Intervention / Treatment
OTHER: Colonoscopy
| Inclusion Criteria:
* 50 to 74 years
* Informed consent signed
Exclusion Criteria:
* Recent digestive symptoms
* Complete colonoscopy less than 5 years ago
* Personal history of colorectal cancer or colorectal adenoma or colonic disease requiring regular colonoscopy surveillance
* Familial history of colorectal cancer in a first degree next of kin before 65 years, or two cases in first degree next of kin.
* Severe extra-intestinal disease
* Screening ill-timed (ex. depression) |
Study Objectives
This study will investigate the drug-drug interactions (DDIs) between rucaparib and oral rosuvastatin (Arm A), and between rucaparib and oral ethinylestradiol and levonorgestrel (Arm B), with rucaparib as a perpetrator.
Intervention / Treatment
DRUG: Rucaparib, DRUG: Rosuvastatin, DRUG: Oral Contraceptives
| Inclusion Criteria (All patients):
* Willing to sign the ICF and to comply with the study restrictions
* Body mass index (BMI) *0 to *0 kg/m2
* Histologically or cytologically confirmed advanced solid tumor
* Patients who, in the opinion of the Investigator, could potentially benefit from treatment with rucaparib
* ECOG performance status less than or equal to 1
* Adequate organ function
Inclusion Criteria (Arm A):
* Male or female patients ≥ 18 years of age
Inclusion Criteria (Arm B):
* Female patients ≥ 18 years of age
Exclusion Criteria (All patients):
* Specific cancer treatments within 14 days prior to Day 1
* Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, acute coronary syndrome, cardiac angioplasty, stenting, or poorly controlled hypertension within the last 3 months prior to screening
* Pre-existing duodenal stent, recent or existing bowel obstruction
* Untreated or symptomatic central nervous system (CNS) metastases. Patients with treated asymptomatic CNS metastases are eligible
* Known HIV or AIDS-related illness, acute or history of chronic hepatitis B or C
* Female patients who are pregnant or breastfeeding
* Participation in another investigational drug trial within 30 days prior to Day 1 or exposure to more than 3 new investigational agents within 12 months prior to Day 1
* Presence of active infection requiring antibiotics
* Active second malignancy
* History of drug abuse (including alcohol)
Exclusion Criteria (Arm A):
* Current use of rosuvastatin or any other statin
* History of hypersensitivity to rosuvastatin
* Current, or history of, clinically significant myopathy
Exclusion Criteria (Arm B):
* Current use of any 1 of the contraceptive drugs or previous contraceptive implants or depot injections, which may still be clinically effective
* History of hypersensitivity to ethinylestradiol or levonorgestrel |
Study Objectives
Recently, targeted next generation sequencing (NGS) platforms have been introduced that allow inexpensive testing for hundreds of mutational hotspots at the same time. A number of additional mutational markers in thyroid cancer have been identified. Highly promising markers associated with tumor prognosis have also been found. This multi-institutional study aims to validate the diagnostic use of mutational markers in thyroid nodules with indeterminate cytology.
The proposed hypothesis is that a broad NGS-based genotyping of thyroid nodules using a large panel of mutational markers applied to thyroid FNA samples can provide an accurate cancer risk stratification in thyroid nodules.
The performance of the panel will be tested in a multi-institutional double-blind prospective study of FNA samples from thyroid nodules with indeterminate cytology and available surgical outcome
Intervention / Treatment
| Inclusion Criteria:
* Patients that undergo a clinically diagnostic thyroid FNA
Exclusion Criteria:
* Children
* pregnant women |
Study Objectives
The main objective of the trial is to document the efficacy of NGR-hTNF administered at low dose weekly in advanced Malignant Pleural Mesothelioma patients previously treated with a pemetrexed-based chemotherapy regimen.
Intervention / Treatment
DRUG: NGR-hTNF plus Best Investigator's Choice (BIC), DRUG: Placebo plus Best Investigator's Choice (BIC)
| Inclusion Criteria:
* Age ≥ 18 years
* Histologically or cytological confirmed malignant pleural mesothelioma of any of the following subtype: epithelial, sarcomatoid, mixed, or unknown
* Prior treatment with no more than one systemic pemetrexed-based chemotherapy regimen administered for advanced or metastatic disease. Prior use of a biological agent in combination with a pemetrexed-based regimen and prior administration of intrapleural cytotoxic agents are allowed. Patients who have previously received anthracyclines should not receive doxorubicin
* ECOG Performance Status 0 - 2
* Life expectancy of ≥ 12 weeks
* Adequate baseline bone marrow, hepatic and renal function, defined as follows:
* Neutrophils ≥ *5 x 109/L; platelets ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL
* Bilirubin ≤ *5 x ULN
* AST and/or ALT ≤ *5 x ULN in absence of liver metastasis or ≤ 5 x ULN in presence of liver metastasis
* Serum creatinine < *5 x ULN
* Measurable or non-measurable disease according to MPM-modified RECIST criteria
* Patients may have had prior therapy providing the following conditions are met:
* Surgery: wash-out period of 14 days
* Systemic and radiation anti-tumor therapy: wash-out period of 28 days
* Patients must give written informed consent to participate in the study
Exclusion Criteria:
* Patients must not receive any other investigational agents while on study
* Patients with myocardial infarction within the last six months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
* Uncontrolled hypertension
* QTc interval (congenital or acquired) > 450 ms
* History or evidence upon physical examination of CNS disease unless adequately treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard medical therapy, or history of stroke)
* Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
* Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
* Pregnancy or lactation |
Study Objectives
The study seeks to determine the prevalence of sleep disordered breathing in a population of patients diagnosed with lung cáncer.
Intervention / Treatment
OTHER: Sleep testing
| Inclusion Criteria:
* All patients with recently diagnosed lung cancer, inlcuding all stages of disease.
Exclusion Criteria:
* Patients unable to comply with home sleep testing. |
Study Objectives
The purpose of this trial is to evaluate the effect of investigational drug nivolumab in combination with either gemcitabine/cisplatin chemotherapy, or in combination with another investigational agent ipilimumab in patients with advanced unresectable biliary tract cancer.
Gemcitabine/cisplatin is the standard of care treatment for biliary tract cancer.
Nivolumab and ipilimumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Nivolumab (Opdivo) is FDA approved for the treatment of several cancers including metastatic melanoma, advanced lung, kidney, head \& neck and bladder cancer. The combination of nivolumab and ipilimumab (Yervoy) is FDA approved for metastatic melanoma.
Intervention / Treatment
DRUG: Gemcitabine, DRUG: Cisplatin, DRUG: Ipilimumab, DRUG: Nivolumab
| Inclusion Criteria:
* Patients must have a pathologically confirmed adenocarcinoma of the biliary tract (intra-hepatic, extra-hepatic (hilar, distal) or gall bladder) that is not eligible for curative resection, transplantation, or ablative therapies. Tumors of mixed histology are excluded.
* Patients may have received prior radiation, chemoembolization, radioembolization or other local ablative therapies or hepatic resection if completed ≥ 4 weeks prior to registration AND if patient has recovered to <= grade 1 toxicity. Extrahepatic palliative radiation is permitted if completed ≥ 2 weeks prior to enrollment AND if patient has recovered to ≤ grade 1 toxicity.
* Patients must have radiographically measurable disease in at least one site not previously treated with radiation or liver directed therapy (including bland, chemo- or radio-embolization, or ablation) either within the liver or in a metastatic site.
* Must be ≥18 years of age
* Must have a Child-Pugh score of A (prognosis in chronic liver disease and cirrhosis)
* Must have an ECOG (Eastern Cooperative Oncology Group) performance status of 0-1
* Ability to understand and willingness to sign IRB-approved informed consent
* Willing to provide archived tissue, if available, from a previous diagnostic biopsy
* Must be able to tolerate CT (computerized tomography) and/or MRI (magnetic resonance imaging) with contrast
* Must have adequate organ function obtained ≤ 2 weeks prior to registration
Exclusion Criteria:
* Patients may not have received prior systemic treatment (chemotherapy or targeted therapy) for advanced BTC (biliary tract cancer). Prior adjuvant chemotherapy is permitted provided it was completed > 6 months from registration.
* Must not have a diagnosis of immunodeficiency, or have received systemic steroid therapy, or any other form of immunosuppressive therapy within 7 days prior to trial treatment.
* Must not have known Hepatitis B, Hepatitis C, or HIV seropositivity. Testing is not required in absence of clinical suspicion.
* Must not have prior history of organ transplantation or brain metastasis.
* Must not have undergone a major surgical procedure < 4 weeks prior to registration.
* Must not have an active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ. Patients with history of malignancy are eligible provided primary treatment of that cancer was completed > 1 year prior to registration and the patient is free of clinical or radiologic evidence of recurrent or progressive malignancy.
* Must have no ongoing active, uncontrolled infections
* Must not have received a live vaccine within 30 days of planned start of the study therapy.
* Must not have a psychiatric illness, other significant medical illness, or social situation which, in the investigator's opinion, would limit compliance or ability to comply with study requirements.
* Women must not be pregnant or breastfeeding since study drugs may harm the fetus or child.
* Women of child-bearing potential and men must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the duration of study participation and for 5 months (for women) and 7 months (for men) following completion of study therapy.
* Participants with an active, known or suspected autoimmune disease which may affect vital organ function, or has/may require systemic immunosuppressive therapy for management are excluded. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
* Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 7 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. |
Study Objectives
Purpose
This study is an 'N-of-one' observational study focusing on individuals with a hereditary predisposition to cancer due to a genetic mutation in the TP53 gene. An individual with this mutation has a \>90% chance of developing many different forms of cancer in their lifetime. Since germline TP53 gene mutation carriers are highly susceptible to cancer, cancer prevention strategies and early cancer detection strategies are crucial. Unfortunately, the current standard of care for monitoring germline TP53 gene mutation carriers for early signs of cancer is yearly MRI scans and intermittent blood draws. Villani et al. showed that standard monitoring is inadequate and introduced a more sophisticated protocol for early cancer detection. We extended the Villani et al. protocol to include a number of markers for early detection and are currently vetting their utility, in terms of their inherent variability, patient tolerability of frequent interrogation, and ability to show changes that might indicate a need for further examination.
In addition to the markers being collected, important covariate information, such as diet, sleep, and activities are being collected (via, e.g., wearable wireless devices) in order to take them into account in assessing the levels of the markers at a single data collection time or over time. One important aspect of the protocol is to identify changes, rather than specific levels, in marker status over time for an individual that might be indicative of tumor formation, essentially exploiting the concept of 'personalized thresholds' discussed by Drescher et al.
If any indication of the presence of a cancer, tumorigenic process, or general sign of ill-health is observed, the protocol calls for a discussion of the findings among the research team, followed by a discussion between the clinical lead on the research team and the primary care provider and/or specialists overseeing a participating patient's care, possible validation of the assay(s) motivating the discussions, and a decision on how to intervene on the part of the primary care provider and/or specialists.
Intervention / Treatment
| Inclusion Criteria:
* Any individual and their family with a known functionally significant germline TP53 mutation susceptible to Li-Fraumeni Syndrome.
* Any individual and their family with a known hereditary cancer syndrome.
Exclusion Criteria:
* No functionally significant germline TP53 gene mutation.
* Inability to tolerate intensive biomonitoring. |
Study Objectives
Nutritional derangements are very common in cancer patients and negatively affect survival, morbidity and quality of life. Intervention trials have demonstrated that nutritional counseling can improve energy balance, nutritional status and quality of life in patients undergoing chemo-radiotherapy. Oxidative stress plays a role in the tumor-cytotoxic effect of cancer chemotherapy and radiotherapy but may also play a role therapy-related adverse events such as an impairment of nutritional status and quality of life. The nutritional properties of whey protein have recently raised attention. In view of the high content in cysteine these proteins can positively stimulate the synthesis of glutathione which, in turn, could contribute to the modulation of whole-body and cellular redox state. However, evidence on the role of this dietary intervention in cancer patients is limited.
Intervention / Treatment
DIETARY_SUPPLEMENT: Whey protein, OTHER: Nutritional counseling
| Inclusion Criteria:
* Cancer patients (lung, gastric, pancreatic, breast, colon, esophageal)
* Eastern Cooperative Oncology Group performance status ≤ 2
* Weight loss >= 10% in the last 6 months
* Chemotherapy
* Written informed consent
Exclusion Criteria:
* Age < 18 years
* Ongoing artificial nutrition (enteral or parenteral)
* Unavailability to planned measurements |
Study Objectives
The purpose of this study was to determine the maximum tolerated dose (MTD) and the recommended dose for future studies of ECO-4601 administered as a continuous IV infusion for 14 days with 7 days recovery (21 day cycle) in patients with histologically confirmed solid tumors (high grade glioma, colorectal, lung, breast, ovarian, pancreatic and prostate). This study was also designed to determine the clinical pharmacokinetic profile, safety of multiple cycles of administration, and document the antitumor activity of ECO-4601.
Intervention / Treatment
DRUG: ECO-4601
| Inclusion Criteria:
* Informed about the study and consent to participate in the study
* Clinically or radiologically documented advanced solid malignancy for which no standard therapy is available, or which has failed standard therapy
* Patients with the following solid tumors: high grade glioma, colorectal, prostate, pancreatic, lung, ovarian and breast carcinoma
* Age ≥ 18 years of age
* ECOG ≤ 2
* Laboratory hematology and biochemistry protocol test result abnormalities ≤ Grade 1, graded using NCI CTCAE version *0
* Patients with no chemotherapy during the 4 weeks preceding patients' first dose of ECO-4601 (day 1, cycle 1)
* No other anticancer treatment during the study
* Patients can be receiving stable or decreasing dose of steroids within 2 weeks prior to patient's signature of the informed consent
* Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre
* Previous Therapy
* Hormonal therapy: Patients may have had prior hormonal therapy provided it is discontinued upon ICF signature
* Radiation: Patients may have had prior radiation therapy. Patients must have recovered from the acute toxic effects of radiotherapy
* Previous surgery: Previous surgery is permitted provided that at least 2 weeks have elapsed between major surgery (non-biopsy) and ICF signature
Exclusion Criteria:
* Patients with brain metastases
* Unlikely to comply with protocol or difficulty to understand the purpose of the study
* Life expectancy < 12 weeks
* Clinically significant co-morbid disease, e.g. renal failure, ischemic vascular disease, uncontrolled seizure, dementia
* Any patient with a potentially curable malignancy who has not yet received appropriate standard therapies
* Anti seizure drugs known inducers of cytochrome P450
* Documented HIV, active hepatitis B or C infections
* Patients with active or uncontrolled infections or with serious illnesses or medical conditions, which would not permit the patient to be managed according to protocol
* Pregnant or lactating women; both men and women enrolled on study should be using adequate birth control measures throughout the course of the study. Women of childbearing potential must have a negative serum or urine pregnancy test documented within 14 days prior to registration and at study start
* Inability or refusal to practice contraception during therapy of ECO-4601, unless patient is surgically sterile or woman is postmenopausal for at least 2 years
* Patients who have been treated with any investigational drug within 4 weeks of patient's signature of informed consent form, or who are receiving concurrent treatment with other experimental drugs or anti cancer therapy
* Patients in whom a proper central line cannot be established
* Concomitant therapy with therapeutic coumadin; patients can be transferred to low molecular weight heparin
* Patients on low molecular weight heparin for < 2 weeks prior to ICF signature
* Polysorbate 80 being a major constituent of ECO-4601 and known to cause hypotension, patients with uncontrolled hypotension will be excluded
* Known hypersensitivity to farnesylated dibenzodiazepinone or any of the formulation components
Concomitant Therapy Permitted:
* Patients may receive ongoing supportive and palliative care (eg: pain control) as clinically indicated throughout the study.
* Patients can be treated with corticosteroids if medically needed
* Usage of low molecular weight heparin is allowed
* Anti seizure products are permitted provided they are not inducers of cytochrome P*
Concomitant Therapy Not Permitted:
* Other anticancer treatment
* Other investigational therapy
* Concomitant therapy with coumadin
* Cytochrome enzyme inducing anti epileptics
* G-CSF, GM-CSF and other growth factors may not be used as a substitute for a scheduled dose reduction; however they may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated at the discretion of the investigator. Use of erythropoietin is allowed if treatment has been initiated for ≥ 2 months. Use of growth factors must be documented on case report forms.
* Hormonal therapy |
Study Objectives
The study will determine the maximum tolerated dose (MTD) of AUY922 given in combination with cetuximab in previously treated patients with KRAS wild-type metastatic colorectal cancer.
Intervention / Treatment
DRUG: AUY922, DRUG: Cetuximab
| Inclusion Criteria:
* Histologically or cytologically confirmed colorectal cancer
* KRAS wild type metastatic colorectal cancer
* Progression of disease on at least 2 prior therapy to have included 5FU, or oxaliplatin or bevacizumab or irinotecan
* Prior treatment with cetuximab is allowed (full dose tolerated), provided that the patient never required a dose reduction due to toxicities
* Must have at least one measurable lesion
* Must be 18 years of age or older
* ECOG performance status 0-1
* Life expectancy must be greater than 12 weeks
* For women of childbearing potential, a negative pregnancy blood test must be obtained less than 3 days prior to the first AUY922 infusion
Exclusion Criteria:
* Colorectal cancer with a KRAS mutation or in which the KRAS genotype status is unknown
* Metastasis to the CNS
* Prior treatment with any Hsp90 inhibitor compounds
* Patients who received systemic anti-cancer treatment prior to the first dose of AUY922 within the following time frames:
* Radiotherapy, conventional chemotherapy: within 2 weeks
* Palliative radiotherapy: within 2 weeks
* Nitrosoureas, monoclonal antibodies, such as trastuzumab and mitomycin: within 6 weeks
* Any continuous-dosing (i.e. daily dosing, every-other-day dosing, Monday-Wednesday-Friday dosing, weekly etc.) of systemic anti-cancer treatment for which the recover period is not known, or investigational drugs (i.e. targeted agents) within a duration of ≤ 5 half lives of the agent and their active metabolites (if any)
* Treatment of therapeutic doses of coumadin-type anticoagulants. \[Maximum daily dose of 2mg, for line patency permitted\]
* Known sensitivity to cetuximab
* Unresolved ≥ grade 1 diarrhea
* Malignant ascites that require invasive treatment
* Concurrent medications that are substrates, inhibitors or inducers of CYP3A4, CYP2C8, CYP2C9 and CYP2C19 and cannot be switched or discontinued or switched to an alternative drug prior to commencing AUY922 dosing need special consideration on a case by case basis
* Major surgery ≤ 2 weeks prior to randomization or who have not recovered from such therapy
* Impaired cardiac function |
Study Objectives
This pilot clinical trial studies how well TracelT hydrogel works in localizing bladder tumors in patients undergoing radiation therapy for bladder cancer. TracelT hydrogel marks the location of a bladder tumor and makes it more visible during imaging tests. Using TracelT hydrogel tissue marker may help doctors learn more about tumor location and altering radiation dosage for bladder cancer.
Intervention / Treatment
DEVICE: Polyethylene Glycol Hydrogel
| Inclusion Criteria:
* Histologically confirmed malignancy of the bladder
* No prior cystectomy
* Treatment plan for bladder must include at least 4 weeks of daily radiation treatment (most patients will receive chemotherapy concurrent with radiation, but this is not required for trial enrollment)
* Patient must undergo TraceIT hydrogel placement within 8 weeks prior to starting radiation therapy for bladder cancer
* Participants must have a complete history and physical examination within 60 days of study entry
* Participants must be able to provide informed consent for treatment and trial participation
* No restrictions on prior treatment to be eligible
Exclusion Criteria:
* Prior cystectomy
* Unable to have TraceIT hydrogel placement < 8 weeks prior to beginning radiation treatment
* Treatment for metastatic bladder cancer |
Study Objectives
To evaluate the effect of collagenase clostridium histolyticum treatment at the Department of Orthopaedic surgery at Horsens Regional Hospital after minimum one-year follow-up (FU).
Intervention / Treatment
DRUG: Xiapex
| Inclusion Criteria:
* dupuytrens disease
* xiapex treatment
Exclusion Criteria:
* demens/other psychiatric diseases |
Study Objectives
The purpose of this study is to evaluate the appropriate timing to do preventive ileostomy closure after total mesorectal excision of rectal cancer. To evaluate the effectiveness and safety of preventive ileostomy closure at different time (12 weeks / 24 weeks after radical resection of rectal carcinoma). This study was expected to demonstrate that the early preventive ileostomy closure after total mesorectal excision of rectal cancer does not increase the risk of complications.
Intervention / Treatment
PROCEDURE: stoma closure at different times
| Inclusion Criteria:
* sign the informed consent
* postoperative pathology is rectal adenocarcinoma
* primary middle and low rectal cancer patients (tumor distance from the anal margin is less than 10 cm)
* underwent total mesorectal excision for rectal cancer with preventive loop ileostomy
Exclusion Criteria:
* postoperative pathology is not rectal adenocarcinoma (rectal neuroendocrine tumor, lymphoma, etc.)
* postoperative pathologic staging of rectal cancer is I phase, II phase
* underwent total mesorectal excision for rectal cancer without preventive loop ileostomy
* emergency operation for rectal cancer
* disease progression (local recurrence or distant metastasis, etc.)
* anastomotic stenosis
* serious system disease, including heart dysfunction, respiratory insufficiency, liver and kidney dysfunction, serious blood diseases
* participate in other clinical trial
* pregnancy or perinatal woman
* combined with other malignant tumor
* with a history of neurological and psychiatric disorders
* patients with abnormal bone marrow suppression after chemotherapy |
Study Objectives
Sleep is essential for human function, immunity, and well-being. In the general population, sleep disturbance and insomnia cause significant health problems and impact on the quality of life of many individuals. The incidence of insomnia in cancer patients is disproportionality higher, with breast cancer patients experiencing prevalence rates ranging from 19% to 69%. The impact of insomnia on cancer patients' lives can be significant and is associated with depression, cancer-related fatigue, increased pain, reduced quality of life, decreased immunity, disease progression, and survival. To date, breast cancer studies show large variation in reported insomnia prevalence rates, and the severity of sleep complaints in these patients have been difficult to assess. Thus, these issues require further investigation using standardised and validated measures.
In this observational study, we aim to investigate the prevalence and severity of insomnia in a cohort of breast cancer patients at the Christie Hospital using the Insomnia Severity Index (ISI), a validated measure for insomnia. This study will consist of two stages. In Stage 1, patients aged 18 and over, who provide informed consent and have a diagnosis of Stage I, II or III breast cancer in the previous 12 months will be asked to complete the validated ISI. Using the ISI, participants identified as having sleeping difficulties and/or insomnia will be invited to Stage 2 of the study. In this stage, participants will be asked to track their sleep each morning for 3 weeks using a digital sleep diary downloaded onto their own smartphone. They will also be asked to complete a series of questionnaires gathering information regarding their quality of life, well-being, and health. This research will provide a better understanding of sleeping patterns, sleeping difficulties and insomnia in patients with breast cancer, and in the long-term, help us design better treatments for patients with sleeping problems.
Intervention / Treatment
OTHER: Stage 2 Digital sleep diary app
| Inclusion Criteria
Stage 1:
* Age > 18 years.
* Informed consent to Stage 1 of the study
* Diagnosis of Stage I, II or III breast cancer within the previous 12 months
Stage 2:
* Informed consent to Stage 2 of the study
* Current Sleep Disturbance; a score of 8 or more on the Insomnia Severity Index.
* History of sleep disturbance prior to the screening/baseline consultation; with beginning or worsening of sleep disturbance since breast cancer diagnosis e.g. sleep problems began or get worse with the diagnosis of breast cancer or with chemotherapy.
* Possession of a suitable smartphone that participant can use independently.
Exclusion Criteria:
Stage 1:
* Participants who have limited or no understanding of spoken and/or written English.
* Other diagnosis of cancer, not including basal cell carcinoma of the skin or cervical carcinoma in situ, within the previous 5 years
Stage 2:
* Co-morbidities incompatible with study participation e.g. that result in a participant being unable to complete daily entries satisfactorily via his/her smartphone.
* Known and/or treated sleep apnoea
* Regular shift work or night work (defined as >1 overnight shift per month)
* Breast feeding |
Study Objectives
The goal of this clinical research study is find the highest tolerated dose of paclitaxel that can be given directly into the liver of patients with advanced cancer involving the liver. Researchers also want to collect descriptive information on any effects the drug may have on tumor tissue.
Intervention / Treatment
DRUG: Paclitaxel
| Inclusion Criteria:
* Patients with histologically confirmed diagnosis of advanced malignancy and liver involvement as dominant site of metastasis.
* Performance status ECOG < or = 2 (Requires occasional assistance but is able to care for own needs).
* Adequate renal function (serum creatinine < *0 mg/dL).
* Adequate hepatic function (Total bilirubin < *0 mg/dL; ALT </= 5 times upper normal reference value).
* Bone marrow function (ANC >or =*5 cells/mcL; PLT > or = 100,000 cells/mcL).
* At least three weeks from previous therapy and complete recovery from all associated acute toxicities.
* Ability to fully read, comprehend, and sign informed consent forms.
* All females in childbearing age must have a negative urine or serum HCG test unless prior hysterectomy or menopause. Women of childbearing potential and men must use effective birth control.
* Patients should be refractory to standard chemotherapy or have no conventional therapy that produces a CR rate of at least 10% or an increase in survival of at least three months.
* Patients of both genders, 13 year-old or older.
Exclusion Criteria:
* Clinical or radiographic evidence of ascites.
* Pregnant or breastfeeding females.
* Hypersensitivity to paclitaxel compounds.
* History of severe hypersensitivity reactions to products containing polyoxyethylated castor oil or Cremophor.
* Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
* Untreatable bleeding diathesis.
* Portal vein thrombosis.
* Peripheral neuropathy > Grade 1 according to NCI CTC v.*0: sensory alteration not interfering with function).
* Untreated (radiation therapy, chemotherapy, surgery or a combination of modalities) brain metastasis. |
Study Objectives
This research study is looking at a new DARPin® drug candidate, called MP0250. There is evidence from preclinical studies that MP0250 may be effective in the treatment of cancer. This is the first study of MP0250 in humans and its main purpose is to test its safety and tolerability in patients with cancer. This study will also examine how the drug is changed by and removed from the body and look for indicators that the drug may be effective against cancer. This study will test several different dose levels of the study drug to determine the safety and tolerability profile of the drug.
Intervention / Treatment
DRUG: MP0250
| Inclusion Criteria:
* Male or female ≥ 18 years
* Histologically confirmed and documented advanced or metastatic solid tumour refractory to at least 1 prior regimen of standard treatment or for which no curative therapy is available and for whom MP0250 is a reasonable option
* Progressive or stable disease documented radiologically in the 4 weeks prior to screening
* Presence of a measurable tumour or a tumour evaluable per RECIST v*1
* ECOG performance status ≤ 1
* Life expectancy ≥ 12 weeks
* Adequate haematological function prior to first dose, defined as:
* Absolute neutrophils count ≥ 1500 cells/μL
* Haemoglobin ≥ 9 g/dL
* Platelet count > 100,000/μL
* Prothrombin time or partial thromboplastin time < *2 x ULN
* Adequate renal function prior to first dose, defined as either
* Serum creatinine < *5 mg/dL or
* Serum creatinine clearance ≥ 50 mL/min/m2 (by Cockroft-Gault equation)
* Adequate hepatic function prior to first dose, defined as
* Total bilirubin ≤ *5 x ULN
* AST/ALT ≤ *5 x ULN, or ≤ 5 x ULN if known hepatic metastases
* Alkaline phosphatase ≤ *5 x ULN, or ≤ 5 x ULN if known hepatic or bone metastases
* Female patients with a negative pregnancy test result at screening and baseline
Exclusion Criteria:
* Female patients pregnant or breast-feeding
* Haematological malignancies or other secondary malignancy, that is currently clinically significant or requires active intervention
* Known untreated or symptomatic brain metastases
* Predominantly squamous non-small cell lung carcinoma
* Anti-tumour treatment within 4 weeks of the first infusion of MP0250, such as chemotherapy, experimental or targeted therapy, biologics, hormonal therapy and radiotherapy. The anti-tumour treatments below need longer wash-out periods and must not be given within the indicated weeks of the first infusion of MP0250:
i. Nitrosoureas: 6 weeks ii. Monoclonal antibodies: 8 weeks
* Exceptions: the following anti-tumour treatments are allowed as indicated i. Palliative radiation to bone metastases to relieve bone pain ii. Standard of care treatment such as bone modifying agents (i.e. bisphosphonates), denosumab, maintenance hormonal therapy for metastatic prostate and breast cancers, hormone-replacement therapy, and oral contraceptives
* Presence of residual toxicities of CTC-AE Grade ≥ 2 after prior anti-tumour therapy at screening. Except meeting other exclusion criteria, grade 1 toxicities related to previous treatments are acceptable at the time of the first infusion of MP0250, as well as Grade 2 alopecia
* Exclusion criterion removed
* Major surgical procedures, open biopsy or significant traumatic injury within 4 weeks of first dose or anticipation of major surgical procedure during the course of the study, core biopsy or minor surgical procedures within 1 week of first dose
* Serious non-healing wound, active ulcer or untreated bone fracture
* Proteinuria at screening as defined by ≥ 1+ on urinalysis dipstick, confirmed by ≥ 1g in 24h urinalysis
* Uncontrolled hypertension or any other serious cardiovascular or cardiac condition as judged by the investigator
* Severe or uncontrolled renal insufficiency |
Study Objectives
Malnutrition is a common problem in cancer patients. It negatively influences patients' prognosis and quality of life. In gastrointestinal patients, it is also caused by insufficient food intake due to dysphagia, lack of appetite, nausea, vomiting, impaired digestion and absorption.
Furthermore, influence of prior oncologic treatment (surgery, chemotherapy, and radiotherapy), have been associated with prolonged hospital stay, more postoperative complications and low survival outcome1-4. So, the proper assessment of nutrition status to detect perioperative malnutrition may allow appropriate nutritional therapy and improve survival5.
However, the important factor which prolongs survival rate is good preoperative nutrition status because it effects the postoperative nutrition outcome. The objective of this study is to correlate the association between pre- and postoperative nutrition status and surgical outcomes.
The Nutrition Alert Form (NAF) is a clinical tool for determining nutritional status. The NAF was modified from Subjective Global Assessment (SGA)6, and it is easy to use and does not require nutritional expertise based on laboratory and physical examination. Therefore, the NAF has been used extensively for screening of malnutrition in hospitalized Thai patients and it can classify the nutritional status into three groups : NAF-A (Normal-Mild malnutrition), NAF-B (Moderate malnutrition), NAF-C (Severe malnutrition)
Intervention / Treatment
| Inclusion Criteria:
* All patients GI cancer
* Elective surgery
Exclusion Criteria:
* Lack of oncologic treatment information before surgery
* No history of recurrent cancer or more than one cancer disease
* Patients who have been diagnosed with Carcinomatosis peritonei during the operation |
Study Objectives
The purpose of this study is to help us to better understand the effects of two different types of surgical techniques on pain and quality of life in patients with precancerous lesions or early stage mouth cancers.
Intervention / Treatment
OTHER: Flexible Fiber-based CO2 Laser, Quality of Life forms, OTHER: electrocautery resection and quality of life forms
| Inclusion Criteria:
* Biopsy proven diagnosis or clinical diagnosis of any benign oral cavity lesion. Pre-surgical biopsy will not be required if lesion is suspected to be benign.
* Biopsy proven diagnosis or clinical diagnosis of premalignant oral cavity lesions (leukoplakia, erythroplakia, lichen planus, dysplasia)Pre-surgical biopsy will not be required if lesion is suspected to be benign.
* Biopsy proven diagnosis of small superficial oral cavity SCC (stage T1N0) requiring resection without the need for neck dissection.
* All pathology will be reviewed at MSK to confirm diagnosis.
* The lesion plus the resection margin should not exceed *0 cm circumferentially.
* Planned to undergo surgical treatment by resection without flap reconstruction and without neck dissection.
* All patients age 18 years of age and older.
* Karnofsky performance score over *
Patients on blood thinners (aspirin or Coumadin) will be asked to stop medications 7 days prior to surgery. In the case of Coumadin, patients are switched to lovenox 7 days prior to surgery and this is stopped the day before surgery. Following surgery aspirin or Coumadin are recommenced 48 hours postop.
Exclusion Criteria:
* Patients with previous Head and Neck radiation
* Pregnant or lactating female patients.
* Patients with oral cavity squamous cell cancer requiring neck dissection |
Study Objectives
Sometimes, cancer comes back after it has been successfully treated-a situation called recurrent cancer. When recurrent cancer is suspected, the standard approach to diagnosis is to perform a combination of imaging tests, such as x-rays, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine scans. Sometimes, however, after performing these tests it still may not be clear whether or not the cancer has come back.
Some studies have shown that a diagnostic imaging test called Positron Emission Tomography/Computed Tomography (PET/CT) may be helpful in the diagnosis of recurrent lung, breast, head and neck, ovarian or esophageal cancer or lymphoma. However, it is not clear if PET/CT can offer better results than standard approaches to diagnosis.
This feasibility study is needed to determine how common it is for a diagnosis of recurrent cancer to be unclear even after standard diagnostic imaging tests have been completed. If the enrollment goal is reached (\~60 patients enrolled in 18 months), a larger clinical trial is being planned to determine if PET/CT is helpful in making the diagnosis of recurrent cancer in situations where standard imaging tests have not been helpful. It is also expected that the results of this feasibility study will help to define exactly which patients should be enrolled in this larger clinical trial of PET/CT.
Intervention / Treatment
OTHER: PET/CT scan
| Inclusion Criteria:
* Patients with a previous history of non-small cell lung cancer, breast cancer, head and neck cancer (not thyroid cancer), ovarian cancer, esophageal cancer, or lymphoma (Hodgkin's or non-Hodgkin's) who have suspected recurrence on history and/or physical exam.
* Conventional imaging (e.g., X-ray, ultrasound, CT, MRI, bone scan) is non-diagnostic.
Exclusion Criteria:
* Age less than 18 years.
* Patient with established recurrence requiring staging of recurrent disease.
* Patients who, at the time of the initial evaluation, have already undergone PET/CT within 6 months prior to registration.
* Unable to lie supine for imaging with PET/CT.
* Pregnant or lactating female.
* Significant concurrent medical problems (e.g., uncontrolled diabetes, active cardiac disease, significant chronic obstructive pulmonary disease) making the patient unfit for further cancer therapy.
* Unable to give informed consent. |
Study Objectives
The purpose of this study is to assess whether treatment with the study drug, panitumumab given concomitantly with every 2 (Q2) week oxaliplatin-based chemotherapy and bevacizumab improves progression-free survival (PFS) compared to treatment Q2-week with oxaliplatin-based chemotherapy and bevacizumab alone. All subjects will receive Q2-week oxaliplatin- or irinotecan-based chemotherapy and bevacizumab. Control arm subjects will not receive concomitant panitumumab therapy.
Intervention / Treatment
DRUG: Oxaliplatin Based Chemotherapy, DRUG: Panitumumab, DRUG: Irinotecan Based Chemotherapy, DRUG: Bevacizumab
| Inclusion Criteria:
* Adenocarcinoma of the colon or rectum
* Metastatic colorectal cancer (mCRC)
* Measurable disease per modified response evaluation criteria in solid tumors (RECIST) criteria
* ECOG performance status of 0 or 1
* Available paraffin-embedded tumor tissue (from primary tumor or metastasis) or unstained slides of paraffin-embedded tissue
* If history of other primary cancer, subject will be eligible only if she or he has:
* Curatively resected non-melanomatous skin cancer;
* Curatively treated cervical carcinoma in situ;
* Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 5 years.
* Adequate hematologic data as follows:
* Absolute neutrophil count (ANC) greater than or equal to *5 x 10\^9 cells/L;
* Platelet count greater than or equal to 100 x 10\^9/L;
* Hemoglobin greater than or equal to *0 g/dL. - Adequate renal function:
* Serum creatinine less than or equal to *5 x upper limit of normal (ULN);
* Urinary protein dipstick of less than 2+ (if urinary dipstick 2+ or greater, then excretion of less than or equal to 1000 mg of protein per day as determined by 24-hour urine collection).
* Adequate hepatic function:
* Alkaline phosphatase less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
* Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)(AST) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
* Alanine aminotransferase (serum glutamic-pyruvic transaminase) (ALT) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
* Bilirubin less than or equal to 2 x ULN. - Competent to comprehend, sign, and date an IRB-approved informed consent form
* Before any study-specific procedure, the appropriate written informed consent must be obtained.
Exclusion Criteria:
* Prior chemotherapy or biologic (i.e., antibody or vaccine) treatment for mCRC disease - Last dose of adjuvant or radiosensitizing chemotherapy less than 6 months before randomization - Radiotherapy within 14 days before randomization
* Elective and/or planned major surgical procedure to be performed during the course of this trial (surgery that arises as needed or necessary during the course of the study, not agreed a priori, will not make the subject ineligible)
* Major surgery within 28 days before randomization
* Central nervous system metastases
* History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest X-ray or CT-scan
* Clinically significant ascites
* Preexisting bleeding diathesis or coagulopathy or the need for full-dose anticoagulation
* Any of the following within 1 year before randomization:
* Myocardial infarction;
* Unstable angina;
* Symptomatic congestive heart failure;
* Serious uncontrolled cardiac arrhythmia;
* Cerebrovascular accident or transient ischemic attack;
* Gastrointestinal ulcer or hemorrhage;
* Hemoptysis;
* Pulmonary embolism;
* Deep vein thrombosis, or other significant thromboembolic event.
* Regular use of non-steroidal anti-inflammatory agents
* Female subject of childbearing potential, not abstinent, and not willing to use contraceptives during the course of the study and for 6 months following the last dose of first-line treatment
* Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to randomization
* Male subject, not abstinent, and not willing to use adequate contraception upon enrollment into this study and for 6 months following the last dose of first-line treatment
* Subject known to be human immunodeficiency virus (HIV) positive
* Subject allergic to panitumumab or any components of panitumumab formulation
* History of any medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results
* Subject unwilling or unable to comply with study requirements
* Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures |
Study Objectives
Peritoneal carcinomatosis (PC) results from the metastasis of a primary cancer of the peritoneum (e.g., appendiceal, ovarian, uterine, colorectal, and gastric cancers) that then disseminates throughout the abdominal cavity. Historically progression to PC was considered terminal and resulted in survival times on the scale of a few months with palliative care being the best option for patients. More recently, cytoreductive surgery (CS) has emerged as a means to prolong and improve patient lives with a median increase in survival of up to \~5 years. It has been reported that for every 10% increase in cytoreduction there is a 5.5% increase in median survival time. In addition to surgical tumor debulking within the peritoneal space, it has also been shown that coupling surgical intervention with hyperthermic intraperitoneal chemotherapy (HIPEC) can have an even greater impact on patient outcomes. Pegsitacianine, a micellar fluorescence agent, exploits the ubiquitous pH differences observed between cancerous and normal tissues. This in turn, provides a highly sensitive and specific fluorescence response after localizing within the tumor microenvironment, thus allowing the detection of primary tumors, their margins, metastatic disease, and tumor-containing lymph nodes.
Intervention / Treatment
DRUG: pegsitacianine
| Inclusion Criteria:
* Imaging and biopsy confirmed metastatic disease of peritoneal origin
Exclusion Criteria:
* Known hypersensitivity or allergy to any component of pegsitacianine
* Tumor locations the surgeon deems unfeasible to image intraoperatively
* Excessive and/or generalized metastatic disease deemed inoperative by the surgeon |
Study Objectives
This is a study comparing the activity of lapatinib versus placebo followed by chemoradiation. This study is designed to explore the effects of lapatinib monotherapy on apoptosis/necrosis, in pre-treatment and post-treatment tumour tissue samples in subjects with locally advanced squamous cell carcinoma of head and neck.
Intervention / Treatment
DRUG: Lapatinib oral tablets, DRUG: Placebo
| Inclusion criteria:
* Willing and able to sign a written informed consent.
* Histologically or cytologically confirmed diagnosis of SCCHN.
* Stage III, IVA and IVB disease will be eligible, who are to receive chemoradiation therapy as primary treatment (total dose ≥ 65 Gy). Subjects with distant metastases (stage IVC) will be excluded.
* Willing and able to have a tumour biopsy taken at screening and a second tumour biopsy taken during lapatinib/placebo administration.
* Male or female ≥18 years of age.
Criteria for female subjects or female partners of male subjects: Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal); Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following:
Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or
Consistent and correct use of one of the following acceptable methods of birth control:
male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; implants of levonorgestrel; injectable progestogen; any intrauterine device (IUD) with a documented failure rate of less than 1% per year; oral contraceptives (either combined or progestogen only); or barrier methods, including diaphragm or condom with a spermicide.
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or *
* Subjects must have adequate haematological, renal and hepatic function. Calculated creatinine clearance ≥50 ml/min as determined by the method of Cockcroft and Gault \[Cockcroft, 1976\] or by the EDTA method.
Absolute neutrophil count ≥1,500/μl, platelets ≥100,000/μl. Haemoglobin ≥9gm/dL (5mmol/L). Aspartate (AST) and alanine transaminase (ALT) less than three times the upper limit of the normal range (ULN).
Total bilirubin ≤*0 mg/dL.
* Left ventricular ejection fraction (LVEF) within the institutional normal ranges as measured by echocardiogram (ECHO) or Multigated Acquisition (MUGA) scans.
* Able to swallow tablet whole or swallow a suspension of the tablet dissolved in water at study inclusion. If necessary, the suspension may be administered via percutaneous endoscopic gastrostomy (PEG), percutaneous jejunostomy tube (JTube), or a nasogastric tube (NG or Dobhoff type tube).
* Life expectancy of at least 6 months as judged by the investigator.
Exclusion criteria:
* Subjects with paranasal sinuses, nasopharyngeal and nasal cavity tumours;
* Subjects who have received prior systemic chemotherapy given with curative intent;
* Subjects who received prior radiotherapy;
* Prior or concurrent treatment with tyrosine kinase inhibitors;
* Use of any investigational agent within 30 days or 5 half-lives, whichever is longer, preceding the first dose of lapatinib;
* Concurrent use of CYP3A4 inducers or inhibitors;
* Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure;
* History of another malignancy within the last 5 years, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in situ carcinoma. History of non-invasive lesion or in-situ carcinoma of head and neck that was successfully treated with surgery, photodynamics or laser, will be permitted;
* Distant metastases, ie Stage IVC;
* Females or males of child-bearing potential who are sexually active, if they do not agree to practice an effective method of contraception. (For example oral contraceptives, IUD or diaphragm plus spermicide);
* Pregnant or lactating females (female patients of childbearing potential will undertake pregnancy testing at screening and during study completion/withdrawal visits);
* Malabsorption syndrome, disease significantly affecting GI function, that could affect absorption of lapatinib;
* History of allergic reactions to appropriate diuretics or antiemetics (e.g. 5-HT3 antagonists) to be administered with platinum-based chemotherapy;
* The investigator considers the patient unfit for the study as a result of the medical interview, physical examinations, or screening investigations;
* Subjects taking any prohibited medication (See Section *2)
Other Eligibility Criteria Considerations:
To assess any potential impact on subject eligibility with regard to safety, the investigator must refer to the following document(s) for detailed information regarding warnings,precautions, contraindications, adverse events, and other significant data pertaining to the investigational product(s) being used in this study: investigator's brochure IB and any IB supplements, and expedited investigator safety reports |
Study Objectives
Primary trial objective in this single arm trial is to assess the safety and tolerability of Selectikine (EMD 521873) given in combination with and local tumor irradiation and to determine whether the maximum tolerated dose (MTD) is reached with EMD 521873 doses of up to 0.45 mg/kg.
Secondary objectives are to evaluate PK, immunogenicity, overall response, changes in tumor marker levels and circulating tumor cell numbers, progression-free survival and overall survival. Also, to evaluate biological/immune responses to EMD 521873.
NSCLC patients have to be stable (PR or SD) after first-line chemotherapy in order to be enrolled. A total of 12 to 24 patients are planned. Patients will remain on the dose throughout the trial. It is intended to administer at least 4 cycles (21 d each), or until progression or 2nd line therapy becomes necessary.
Intervention / Treatment
BIOLOGICAL: EMD 521873
| Inclusion Criteria:
* Histologically or cytologically confirmed NSCLC stage IIIb with malignant pleural effusion or stage IV
* Pulmonary primary tumor or at least one NSCLC metastasis in the lung measuring at least 1 cm in diameter and eligible for local radiation with 20 Gy
* Disease control (partial remission or stable disease) after 4 cycles of platinum-based first-line chemotherapy whereby the time between the last dose of first-line chemotherapy and start of trial treatment should not be longer than 8 weeks
* Male or female, aged ≥18 years of age
* Signed written informed consent
* Effective contraception for male and female subjects of childbearing age
* ECOG performance status 0 or 1
* Adequate hematological function defined by WBC ≥3 x 10\^9/L, neutrophils ≥*5 x 10\^9/L, lymphocyte count ≥*5 x 10\^9/L, platelet count ≥100 x 10\^9/L; hemoglobin ≥9 g/dL
* Estimated creatinine clearance ≥50 mL/min according to the Cockcroft - Gault formula or 24-h urine sampling
* Adequate hepatic function defined by a total bilirubin level ≤*5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 x ULN
Exclusion Criteria:
* Requirement for immunosuppressive treatment with the exception of inhalative corticosteroids or low-dose systemic corticosteroids (prednisone equivalent dose ≤10 mg/day)
* Systemic autoimmune disease (e.g. lupus erythematodes, rheumatoid arthritis)
* Organ transplant recipients
* Active infections (including HIV, hepatitis B and C, tuberculosis)
* Known or clinically suspected brain metastases
* Active cardiovascular/cerebrovascular disease (e.g. symptomatic coronary vascular disease, congestive heart failure ≥ NYHA II, LVEF <50%, ventricular arrhythmia requiring medication, myocardial infarction or stroke) within previous 6 months
* Pericardial effusion
* Major impairment in pulmonary function: forced expir¬atory volume in 1 second (FEV1) <50% and diffusion capacity for carbon monoxide (DLCO) <50% of normal limit
* Any other significant disease that in the Investigator's opinion would exclude the subject from the trial
* Known conditions associated with necroses of non-tumor bearing tissues (e.g. esophageal or gastroduodenal ulcers, ischemic bowel disease, chronic inflammations)
* Pregnancy or lactation
* Radiotherapy, chemotherapy, major surgery, biological therapy or any investigational drug within 30 days prior to the start of trial treatment
* Requirement for concurrent systemic anticancer treatment (chemotherapy, biological therapy)
* Pretreatment with anti-EGFR antibodies or tyrosine kinase inhibitors
* Participation in another interventional clinical trial within the past 30 days before start of trial treatment
* Known alcohol or drug abuse
* Any psychiatric condition that would prohibit the understanding or rendering of the informed consent
* Legal incapacity or limited legal capacity |
Study Objectives
The objectives of this study is to investigate treatment patterns and outcomes for Sutent and Inlyta in mRCC patients in a nationwide population-based setting in Sweden.
Intervention / Treatment
DRUG: sunitinib, DRUG: axitinib
| Inclusion Criteria:
* all patients aged ≥ 18 years with at least one filled prescription of an oral targeted therapy relevant for treating mRCC registered in the Swedish Prescribed Drug Register (PDR) between July 1st 2005 and June 30th * The Anatomical Therapeutic Chemical (ATC) codes for the oral drugs relevant for treating mRCC are the following: L01XE04 (sunitinib), L01XE05 (sorafenib), L01XE11 (pazopanib), L01XE17 (axitinib), L01XE10 (everolimus), L01XE26 (cabozantinib), L01XE34 (tivozantib), L01XE29 (lenvatinib).
* The patients identified in the PDR that also are identified in the SCR with the International Classification of Diseases and Related Health Problems (ICD)-7 diagnosis codes I800 or I809 and ICD-10 codes C*0 and C*9 from January 1st 2000 until December 31st 2019;excluding ICD-7 code I801 (cancer of the renal pelvis) will be included in the analysis set.
Exclusion Criteria:
Patients with ICD-7 code I801 will be excluded |
Study Objectives
This study was designed in two phases: Phase I is designed to confirm that the surgeon is able to perform accurate liver surface registration including standard liver features used as landmarks during a scheduled laparoscopic liver ablation procedure and acquires a level of comfort with the procedure.
The surface of the liver will be manually swabbed with the study tracked laparoscopic probe with landmarks noted during data collection. After registration of the liver is obtained, the registration points obtained during this procedure will be evaluated by the surgeon by moving the tracked laparoscopic probe over the liver surface and evaluating the location of the tracked laparoscopic probe displayed on the guidance system three dimensional (3D) image. The surgeon will accept or reject the registration accuracy.
The hypothesis is that the surgeon will be able to successfully acquire liver surface registrations with a small learning curve for technique and will be able to proceed to Phase II of the study.
Phase II contains the registration process included above but adds the additional process of tracking the ablation probe used to perform tumor ablation by attaching the Pathfinder Multi-Tool adaptor and collecting data showing the location of the ablation probe as tracked and displayed on the Pathfinder three dimensional (3D) image.
The surgeon will use ultrasound (US) guidance to locate tumor location during the laparoscopic procedure. The images collected during this process will be recorded by Pathfinder.
Intervention / Treatment
| Inclusion Criteria:
* Scheduled for laparoscopic liver ablation procedure
* Had a preoperative CT image that includes the liver
Exclusion Criteria:
* Severe cirrhosis of the liver
* Kidney failure or dialysis
* Unable to consent |
Study Objectives
The purpose of this trial is to investigate if maintenance DCVAC/OvCa after second-line chemotherapy of carboplatin/gemcitabine or carboplatin/paclitaxel improves efficacy outcomes in women with FIGO stage III and IV epithelial ovarian carcinoma who experienced relapse more than 6 months after complete remission of first line platinum-based chemotherapy (platinum sensitive ovarian cancer)
Intervention / Treatment
BIOLOGICAL: DCVAC/OvCa, DRUG: Standard of Care Chemotherapy
| Inclusion Criteria:
* Patients with histologically confirmed FIGO stage III or IV epithelial ovarian, primary peritoneal or fallopian tube carcinoma (serous,endometrioid, or mucinous) who had complete remission after first-line platinum-based chemotherapy
* Radiologically confirmed relapse after >6 months of remission ( platinum-sensitive cancer)
* Laboratory parameters per protocol
Exclusion Criteria:
* FIGO I, II epithelial ovarian cancer
* FIGO III, IV clear cells epithelial ovarian cancer
* Non-epithelial ovarian cancer
* Borderline tumors ( tumors of low malignant potential)
* Prior or current systemic anti-cancer therapy for ovarian cancer (chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitory therapy, vascular endothelial growth factor or hormonal therapy) except first-line Pt based chemotherapy ( with or without bevacizumab)
* fertile women of child-bearing potential not willing to use a highly effective method of contraception or a combination of methods
* Pregnant of lactating women
* Pre-defined co-morbidities
* Known hypersensitivity to any constituent of DCVAC/OVCa or the selected chemotherapy compounds |
Study Objectives
This a first-in-human study of an antibody blocking the function of the oncogene c-met in patients with cancer.
Intervention / Treatment
DRUG: ARGX-111
| Inclusion Criteria:
* Written informed consent.
* Age ≥ 18 years.
* Performance status of 0 or *
* Histological diagnosis of malignancy.
* Cancer relapsing after, or refractory to standard therapy.
* Malignancy over-expressing the c Met protein.
* Presence of circulating tumor cells (CTCs).
* At least one tumor lesion > 2 cm on PET/CT.
* Serum albumin > 35 g/L.
* Absolute neutrophil count (ANC) > *0 x 109/L.
* Hemoglobin > 90 g/L (*9 g/dL).
* Platelet count ≥ 75 x 109/L.
* Coagulation parameters ≤ *5 x ULN.
* Total bilirubin ≤ *5 x upper limit of normal (ULN).
* Creatine Phosphokinase (CPK) ≤ *5 x ULN.
* Serum creatinine ≤ *5 x ULN.
* Ability to comply with protocol-specified procedures/evaluations and scheduled visits.
Exclusion Criteria:
* History or clinical evidence of neoplastic central nervous system (CNS) involvement.
* Major surgery within 4 weeks of ARGX 111 first dose administration.
* Systemic glucocorticoid administration at doses greater than physiological replacement (prednisone 20 mg equivalent) within 3 weeks of ARGX 111 first dose administration.
* Cytotoxic chemotherapy within 3 weeks of ARGX 111 first dose administration.
* Radiation therapy with curative intent within 3 weeks of ARGX 111 first dose administration.
* Biological therapy (monoclonal antibodies) within 4 weeks of ARGX 111 first dose administration.
* Biological therapy (other than monoclonal antibodies) within 5 half-lives of ARGX 111 first dose administration.
* Unresolved Grade 3 or 4 toxicity from prior therapy, including experimental therapy.
* History of recurrent Grade 3 or 4 toxicity from anti c Met therapy.
* Uncontrolled diabetes, defined as fasting glycemia > 150 mg/dl).
* Active, untreated viral, bacterial, or systemic fungal infection.
* Any clinical finding, including psychiatric and behavioral problems, which, in the opinion of the Investigator, precludes the patient from safely participating in the study.
* Childbearing potential (unless using an adequate measure of contraception).
* Pregnancy or lactation.
* History of severe (Grade 3 or 4) hypersensitivity to recombinant proteins. |
Study Objectives
This is a three-part open label phase 1 study designed to determine the safety profile, MTD, PK and tumor and biomarker response after IT or IV administration of a single dose of VSV-IFNβ-NIS, or combined IT followed by IV VSV-IFNβ-NIS, with or without IV avelumab every two weeks, in patients with refractory advanced/metastatic solid tumors.
Intervention / Treatment
BIOLOGICAL: VSV-IFNβ-NIS, BIOLOGICAL: VSV-IFNβ-NIS and avelumab
| Inclusion Criteria:
* Be > 18 years of age on day of signing informed consent.
* Have a histologically confirmed diagnosis of an advanced and/or metastatic solid tumor that is relapsed and/or refractory to standard therapy, as defined as progression on at least one prior line of therapy in the relapsed/metastatic setting and no existing options are felt to provide clinical benefit.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or *
* Adequate hematological, liver and kidney function.
* Must be willing to implement contraception throughout study and for 120 days after receiving the study drug.
Exclusion Criteria:
* Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever is longer) of the start of study treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of study treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of study treatment.
* Has a history of a bone marrow or solid organ transplant.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. |
Study Objectives
The primary objective of this extension protocol is to evaluate the early safety of a new schedule of NGR-hTNF given weekly, instead of every 3 or 4 weeks, in a cohort of 12 patients randomized to the experimental arm A, as compared to a reference cohort of 12 patients randomized to an anthracycline alone
Intervention / Treatment
DRUG: NGR-hTNF, DRUG: Pegylated liposomal doxorubicin, DRUG: Doxorubicin
| Inclusion Criteria:
* Age ≥ 18 years
* Histologically-proven ovarian cancer, fallopian tube and primary peritoneal cancer in advanced or metastatic stage
* Patients previously treated with a maximum of two platinum-based regimen plus paclitaxel and with documented progressive disease on treatment (refractory patient population) or within 6 months from last chemotherapy cycle (resistant patient population)
* ECOG Performance status 0 - 2
* Life expectancy of 12 weeks or more
* Normal cardiac function and absence of uncontrolled hypertension
* Adequate baseline bone marrow, hepatic and renal function defined as follows:
* Neutrophils ≥ *5 x 109/L; platelets ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL
* Bilirubin ≤ *5 x ULN
* AST and/or ALT ≤ *5 x ULN in absence of liver metastasis or ≤ 5 x ULN in presence of liver metastasis
* Serum creatinine < *5 x ULN
* At least one (not previously irradiated) target lesion or non-measurable disease only, according to RECIST criteria
* Patients may have had prior therapy providing the following conditions are met:
* Surgery and radiation therapy: wash-out period of 14 days
* Systemic anti-tumor therapy: wash-out period of 21 days
* Patients must give written informed consent to participate in the study
Exclusion Criteria:
* Patients must not receive any other investigational agents while on study
* More than two previous chemotherapy lines and previous treatment with anthracycline
* Patients with myocardial infarction within the last six months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
* Prolonged QTc interval (congenital or acquired) > 450 ms
* History or evidence upon physical examination of CNS disease unless adequately treated
* Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
* Known hypersensitivity/allergic reaction or contraindications to human albumin preparations or to any of the excipients
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
* Pregnancy or lactation |
Study Objectives
RATIONALE: CP-724,714 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.
PURPOSE: Phase I trial to study the effectiveness of CP-724,714 in treating patients who have metastatic HER2-overexpressing breast cancer.
Intervention / Treatment
DRUG: CP-724,714
| Inclusion Criteria:
* Histologically or cytologically confirmed HER2-overexpressing breast cancer
* Prior or newly documented HER2 amplification by fluorescence in situ hybridization (FISH)
* Progressive metastatic disease
* Must have received at least one prior chemotherapy regimen for metastatic breast cancer
* At least 1 measurable or evaluable lesion
* At least 1 lesion accessible for 2 separate core biopsies for pharmacodynamic evaluation
* 18 and over
* Male or female
* ECOG 0-1
* Life expectancy, More than 3 months
* Hematopoietic
* Absolute neutrophil count at least 1,500/mm\^3\*
* Platelet count at least 100,000/mm\^3\* NOTE: \*Without hematopoietic growth factors or transfusions
* Hepatic
* Bilirubin no greater than *5 mg/dL
* AST/ALT no greater than *5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
* Renal
* Creatinine no greater than *5 times ULN OR
* Creatinine clearance at least 60 mL/min
* Cardiovascular
* 12-lead ECG with normal tracing
* history of cardiovascular disease (i.e., ischemic heart disease, arrhythmia, or congestive heart failure) unless asymptomatic for the past year with no requirement for antiarrhythmics or a clinically significant medical management change
* Gastrointestinal
* Able to take oral medication\* Negative pregnancy test
* Fertile patients must use effective contraception
* At least 4 weeks since prior trastuzumab (Herceptin)
* At least 4 weeks since other prior biologic therapy or immunotherapy
* At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas)
* At least 6 months since prior doxorubicin or doxorubicin equivalents without any prior or developing signs or symptoms of cardiomyopathy
* No cumulative doses of more than 300 mg/m\^2
* At least 2 weeks since prior hormonal therapy for the primary disease
* Concurrent hormone replacement therapy or luteinizing hormone-releasing hormone agonists allowed
* At least 4 weeks since prior radiotherapy
* At least 3 weeks since prior major surgery (2 weeks for minor surgery)
* Recovered from prior therapy
* At least 4 weeks since prior investigational treatment
* Coumarin or heparin derivatives allowed for the prevention of deep vein thrombosis or port patency
Exclusion Criteria:
* known or clinically suspected brain metastases or leptomeningeal disease
* symptomatic edema or third-space fluid (e.g., ascites or pleural effusions)
* known hepatitis B or C infection
* significant ECG changes that require medical intervention
* QTc interval less than 460 msec
* No history of torsade or other symptomatic QTc abnormality
* LVEF greater than 50% by MUGA
* gastrointestinal abnormality that would require medications (including all antacids)
* persistent symptoms of an esophageal or digestive disorder
* pregnant or nursing
* known HIV infection
* active infection
* concurrent uncontrolled systemic disorders or laboratory abnormalities that would preclude study drug safety evaluation
* mental disorder that would preclude study compliance or ability to give informed consent
* No more than 2 prior trastuzumab-based regimens for advanced disease
* concurrent immunotherapy
* more than 1 prior anthracycline- or anthracenedione-containing regimen (except with approval of the sponsor)
* prior high-dose chemotherapy with hematopoietic stem cell transplantation
* concurrent anticancer chemotherapy
* No concurrent anticancer hormonal therapy, including tamoxifen
* prior radiotherapy to the only disease site that would be assessed for response
* concurrent radiotherapy
* prior partial or complete gastrectomy
* concurrent antiarrhythmics
* concurrent antacids
* concurrent anticoagulant at therapeutic doses
* other concurrent experimental anticancer medications for breast cancer |
Study Objectives
Postoperative nausea and vomiting ( PONV ) is one of the common complications after general anesthesia while genetic factors may play an important role in Postoperative nausea and vomiting. In this study, the investigators investigated the relationship between gene polymorphism ( such as single nucleotide polymorphism ) of the gene HTR3A ( 5-hydroxytryptamine receptor 3A ), HTR3B ( 5-hydroxytryptamine receptor 3B ), HTR3C ( 5-hydroxytryptamine receptor 3C ) and TACR1 ( tachykinin receptor 1 ) etc. with nausea and vomiting after general anesthesia. Simultaneously, the investigators explored the influencing factors of nausea and vomiting.
Intervention / Treatment
| Inclusion Criteria:
* Undergoing breast surgery with general anesthesia
* American Society of Anesthesiologists Physical Status Classifications 1-2
* No history of smoking
* body mass index (BMI) <35 kg/m2
Exclusion Criteria:
* Declined to participate
* Had used antiemetics, steroids, H2 antagonists, anticholinergics, antihistamines, butyrophenones, phenothiazines, metoclopramide or opioids within 24 hours
* Gastroesophageal reflux, gastrointestinal obstruction or ulcer, vestibular or hearing dysfunction
* Liver impairment, renal impairment, psychiatric disorder, chronic pain
* Pregnant and lactating patients
* Requiring postoperative patient-controlled analgesia
* Requiring prophylactic use of antiemetics
* Allergic to drugs related in the study
* Receiving chemotherapy within one week before surgery |
Study Objectives
Multi-center prospective pilot trial study
Intervention / Treatment
DEVICE: artificial intelligence dietary android mobile application
| Inclusion Criteria:
* Possessing smartphone and is willing to use smartphone application
* Been referred to dietitian in outpatient clinic
* At least 18 years of age
* Malaysian
Exclusion Criteria:
* Inability to use the smartphone application (eg. due to vision problems)
* Not been referred to dietitian in outpatient clinic
* Patients who participate in other study at the same time
* On nutrition support (enteral / intra-venous)
* Vulnerable subjects |
Study Objectives
The purpose of the study is to evaluate the efficacy of Seprafilm and guardix in reducing the incidence of bowel obstruction and to evaluate the incidence of all serious adverse events (SAEs) associated with the use of Seprafilm and guardix occurring within 30 days postoperatively.
Intervention / Treatment
PROCEDURE: Guardix, PROCEDURE: Seprafilm
| Inclusion Criteria:
* Clinical diagnosis of GI cancer
* Operable
Exclusion Criteria:
* Withdrew consent
* Pregnant
* Ascites
* Distant metastasis
* Liver dysfunction (serum total bilirubin >*0 mg/dL)
* Renal failure (serum creatinine >*5 mg/dL)
* A past history of small bowel obstruction. |
Study Objectives
This pilot clinical trial studies comprehensive gene sequencing in guiding treatment recommendations in patients with metastatic or recurrent solid tumors. Studying samples of blood and tissue from patients with cancer in the laboratory may improve the ability to plan treatment.
Intervention / Treatment
OTHER: cytology specimen collection procedure, OTHER: laboratory biomarker analysis
| Inclusion Criteria:
* Are able to understand and provide written informed consent (most recent patient informed consent form) prior to initiation of any study-specific procedures
* Patients are diagnosed with recurrent or metastatic a solid tumor cancer; the first patients to be enrolled will have a diagnosis of breast cancer (Cohort 1) or colorectal cancer (Cohort 2)
* Patients may enter this study at any line of therapy
* Patients must have a tumor sample available for NGS testing
* Patients are within 10 weeks of starting their current line of therapy and enrolled before their 1st computed tomography (CT) scan
* Have an expected survival of >= 3 months, as estimated by the treating oncologist
* Have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2
Exclusion Criteria:
* Are pregnant or nursing women
* Are unable to comply with requirements of the study
* Have a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection |
Study Objectives
This is an open-label, single institution, phase II study of Sorafenib in combination with docetaxel and carboplatin in patients with advanced non-small cell lung cancer. Docetaxel and carboplatin will be given on day 1 of every three week cycle. Patients will take Sorafenib twice a day on the 1st day of treatment and continue to take the medication every day until progression of disease, prohibitive toxicity, or patient withdrawal from the study. Chemotherapy courses will repeat every 21 days in the absence of disease progression or unacceptable toxicity for a total of four cycles.
Intervention / Treatment
DRUG: Sorafenib + Docetaxel/Carboplatin
| Inclusion Criteria:
* Histologically or cytologically confirmed NSCLC with clinical or radiological evidence of advanced disease (Stage IIIB/IV)
* Uni-dimensionally measurable disease
* Age => 18 years
* ECOG performance status of 0-1
* Life expectancy > 3 months
Exclusion Criteria:
* Small-cell or mixed histologies including a small cell component
* Prior chemotherapy, biotherapy, radiotherapy to an area of measurable disease
* Patients with peripheral neuropathy grade => 2 |
Study Objectives
The purpose of this study is to allow patients to receive VELCADE™ (bortezomib) for Injection who experienced progressive disease(PD) while receiving high-dose dexamethasone from the M34101-039 study.
Intervention / Treatment
DRUG: bortezomib
| Inclusion Criteria
* Patient experienced PD, as defined by SWOG+ criteria during or after treatment with high-dose dexamethasone in MPI Study M34101-039, but has not received alternate anti-neoplastic therapy. Intolerance to high-dose dexamethasone therapy as administered in MPI study M34101-039 does not qualify as PD.
* Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
* Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
* Female patient is post-menopausal, surgically sterilized, or willing to use acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) from Screening through the End of Treatment visit.
* Male patient agrees to use an acceptable barrier method for contraception from Screening through the End of Treatment visit.
* Patient meets the following pretreatment laboratory criteria at and within 14 days before Baseline (Day 1 of Cycle 1, before study drug administration). (Note that the End of Treatment assessments of MPI study M34101-039 may qualify as the Screening assessments for MPI study M34101-040 if performed within 14 days of the Baseline visit.):
* Platelet count ≥20 X 10E+9/L, with or without transfusion support.
* Hemoglobin ≥*0 g/dL, with or without transfusion support.
* Absolute neutrophil count (ANC)≥*5 x 10E+9/L, without growth factor support.
* Serum calcium <14 mg/dL (*5 mmol/L).
* Aspartate transaminase (AST):≤*5 x the upper limit of normal (ULN).
* Alanine transaminase (ALT):≤*5 x the ULN.
* Total bilirubin:≤*5 x the ULN.
* If calculated or measured creatinine clearance: ≥20 mL/minute, assessments are as specified in the protocol. If calculated or measured creatinine clearance is <20 mL/minute.
Exclusion Criteria
* Patient participated in M34101-039 and did not have confirmed PD. Dexamethasone intolerance does not qualify as PD.
* Patient had PD on the dexamethasone arm of the MPI Study M34101-039, and then received alternate anti-neoplastic therapy.
* Patient has not recovered from dexamethasone-related toxicity experienced during MPI Study M34101-*
* Patient is known to be human immunodeficiency virus (HIV)-positive.(Patients assessed by the investigator to be at risk for HIV infection should be tested in accordance with local regulations.)
* Patient is known to be hepatitis B surface antigen-positive or has known active hepatitis C infection.(Patients assessed by the investigator to be at risk for hepatitis B or C infection should be tested in accordance with local regulations.)
* Female patient is pregnant or breast-feeding.
* Patient developed a new or experienced worsening of an existing illness during or after completion of Study M34101-039 that, in the investigator's opinion, may put the patient at risk of participation in this study. |
Study Objectives
The purpose of this study is to determine whether or not there are more complications in the extraperitoneal compared with the transperitoneal approach for laparoscopic aortic lymphadenectomy for the surgical staging of endometrial or ovarian cancer
Intervention / Treatment
PROCEDURE: Extraperitoneal Laparoscopic aortic lymphadenectomy, PROCEDURE: Transperitoneal Laparoscopic aortic lymphadenectomy
| Inclusion Criteria:
* Diagnosis of endometrial cancer confirmed by histopathological analysis (endometrial biopsy) requiring surgical staging according to FIGO (the International Federation of Gynecology and Obstetrics) recommendations
* Diagnosis of ovarian cancer confirmed by histopathological analysis after an initial cystectomy or oophorectomy without suspicion of neoplasia thus requiring additional surgical staging according to FIGO recommendations
Exclusion Criteria:
* Diagnosis of advanced endometrial cancer based on findings on imaging techniques (CT, MRI and/or PET)
* Diagnosis of advanced endometrial or ovarian cancer based on intraoperative findings (e.g. peritoneal carcinomatosis at initial laparoscopy)
* Patients who underwent previous aortic lymphadenectomy
* Patients who received previous pelvic and/or aortic radiotherapy |
Study Objectives
The incidence of testicular germ cell tumors, the most common cancer in men aged 15 to 45 years, has doubled in France in 30 years. Reasons remain unclear but a role of environmental factors, especially during critical periods of development, is strongly suspected. Reliable data on environmental exposure during this critical period are sparse.The discordant findings and the limitations of available studies underline the importance to conduct studies with sufficient statistical power to detect risk due to exposures during critical windows of vulnerability.
We conduct a multicentric case-control study to assess this association. Cases and controls will be enrolled during a 18-month period. They will be interviewed by professional telephone interviewers about their occupational and residential history and about their domestic exposure to pesticides and other nuisances.
An optional biological study to assess genetic polymorphisms known to be associated with testicular cancer will be proposed to every cases and controls.
Mothers (or close relative) of cases and controls will also be contacted (with son's agreement). If they agree to participate, they will also be interviewed about antenatal and early life exposure of their sons to pesticides and other nuisances.
Cases will be matched up with 2 controls (one of each group) both on age (+/- 2 years) and on recruiting center.
Intervention / Treatment
OTHER: Phone interview and blood test
| Inclusion Criteria:
* Men aged between 18 and 44 years old
* Born in metropolitan France
* Able to understand, read and write French
* Without any psychiatric and severe cognitive disorder
* Willingness to participate to the study
* Who has signed and dated an inform consent form
* Affiliated to a health care system
Exclusion Criteria:
* Who has a legal guardian
* History of testicular germ cell tumor or cryptorchidism (only for controls) |
Study Objectives
SB497115 is an oral agent which activates the thrombopoietin receptor and increases platelet counts in healthy volunteers. This study is examining several different doses of SB497115 versus placebo as treatment for patients with advanced solid tumors scheduled to receive chemotherapy with carboplatin and paclitaxel every 21 days. Patients will receive SB497115 on days 2-11 of each 21 day cycle for at least 2 cycles of chemotherapy and for a maximum of 8 cycles of chemotherapy.
Intervention / Treatment
DRUG: SB497115, OTHER: Placebo
| Inclusion criteria:
* Subjects ≥18 years old, who are chemotherapy naïve, with histologically or cytologically confirmed advanced solid tumor (leukemia and lymphoma are excluded) who are scheduled to received carboplatin/paclitaxel as shown below. For the purpose of this study, advanced tumors are defined as tumors that are being treated with palliative intent (i.e., not being treated with curative intent).
* Subjects scheduled to receive first-line chemotherapy as carboplatin AUC 5-6 IV over 30 minutes plus paclitaxel 175-225 mg/m2 IV over 3 hours on day 1 every 21 days, with routine pre-medications, i.e., 20 mg dexamethasone \[or equivalent\] orally 6 and 12 hours pre-paclitaxel, 50 mg IV diphenhydramine \[or equivalent\] and 300 mg IV cimetidine \[or equivalent\] 30-60 minutes pre-paclitaxel.
* ECOG-Zubrod performance status is 0, or *
* Subject has no history of platelet disorders or dysfunction and no history of a bleeding disorder.
* Subjects have adequate:
hematologic function (ANC ≥ 1,500/mm3, hemoglobin ≥ 9 g/dL, and platelet count ≥100,000/mm3 and < upper limit of normal range (eg, 400,000 to 450,000/mm3), hepatic function (bilirubin ≤ 2 mg/dL and alanine aminotransferase ≤ three times the upper limit of normal), renal function (creatinine ≤ *0 mg/dL).
* Subject has no physical limitation to ingest and retain oral medication.
* Subject has life expectancy of at least 6 months.
* Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must either be of nonchildbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use one of the following acceptable methods of contraception from two weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:
Complete abstinence from intercourse; Intrauterine device (IUD); Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide); Male partner is sterile prior to entry into the study and is the only partner of the female; Systemic contraceptives (combined or progesterone only).
* Subject is able to understand and comply with protocol requirements and instructions and intend to complete the study as planned.
* Subject has signed and dated written informed consent.
* Chemotherapy naive patients with advanced solid tumors (without brain metastasis or rapid progression within 2 weeks) who are scheduled to receive standard first-line therapy with carboplatin and paclitaxel every 21 days.
* Adequate hematologic, hepatic and renal function.
Exclusion criteria:
* Any clinically relevant abnormality, other than cancer, identified on the screening examination, or any other medical condition or circumstance, which in the opinion of the Investigator, makes the subject unsuitable for participation in the study and/or would make the patient's data difficult to interpret.
* Subjects with a known history of rapidly progressive disease (marked increase in tumor size \[>50%\], ascites, or serious symptoms related to underlying cancer in the preceding 4-week period), surgery within the previous 2 weeks, radiotherapy within the previous 4 weeks, or any prior chemotherapy.
* Subjects with known pre-existing cardiac disease, including congestive heart failure, arrhythmias requiring treatment, or myocardial infarction within the preceding 3 months.
* Subjects with abnormal resting 12-lead ECG at screening that would indicate preexisting cardiac disease, as noted in exclusion criterion *
* Subjects with known clotting disorder associated with hypercoaguability.
* Subject has consumed aspirin, aspirin-containing compounds, salicylates, quinine or non-steroidal anti-inflammatories (NSAIDs) for > 3 consecutive days within 2 weeks of the study start and would require them at any time during the study.
* Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
* Subject has consumed liquid antacids (e.g. Maalox, Mylanta, Amphogel, milk of magnesia), chewable antacids (e.g. TUMS) or calcium supplements within 48 hours of the first dose of study medication, and/or will require these medications during the study.
* Subject has consumed rosuvastatin or pravastatin within 1 week of the first dose of study medication and/or will require these medications at any time during the study.
* Any history of drug-induced thrombocytopenia (e.g., quinine).
* Systemic anti-coagulant use within 4 weeks prior to study entry.
* Consumption of any herbal or dietary supplements, excluding vitamin or mineral supplements (See Exclusion 8 for calcium supplements), within 1 week of the study start.
* Female subjects who are lactating or have a positive beta-hCG at screening.
* Subjects with a history of CNS metastases or clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by CT or MRI brain scan.
* History of platelet or bleeding disorders.
* Patients using aspirin, aspirin-containing compounds, salicylates, antacids, rosuvastatin, pravastatin, non-steroidal anti-inflammatory drugs for greater than 3 days during and within 3 weeks prior to the study.
* Females who are pregnant or breastfeeding. |
Study Objectives
This is a multi-center, phase 1, open-label first-in-human study of AMG 319 in subjects with relapsed or refractory lymphoid malignancies. This study consists of two parts. The dose exploration in part 1, studies cohorts of 3 subjects with relapsed or refractory lymphoid malignancies and uses a practical continuous reassessment model \[CRM\] to guide dose escalation and to define the MTD. The dose expansion in part 2 will enroll 20 subjects with CLL at a dose no higher than the MTD and further explore the safety, PK, and clinical activity of AMG 319 in this patient population.
Intervention / Treatment
DRUG: AMG 319
| Inclusion Criteria:
* Part 1 (Dose Exploration): Relapsed or refractory lymphoid malignancy of the following type for which standard treatment does not exist or is no longer effective:
B-cell Chronic Lymphocytic Leukemia (CLL) confirmed by immunophenotype or Non-Hodgkin Lymphoma: Low or intermediate grade B-cell NHL, mantle cell lymphoma, non-cutaneous T-cell NHL confirmed by histology and/or immunophenotype
* Part 2 (Dose Expansion): Subjects must have relapsed or refractory B-cell Chronic Lymphocytic Leukemia confirmed by immunophenotype for which standard treatment does not exist or is no longer effective.
* Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
* Life expectancy of > 3 months, in the opinion of the investigator
* Men or women ≥ 18 years old
* Hematological function, as follows:
Absolute neutrophil count (ANC) ≥ *5 x 109/L (unless due to disease-related bone marrow involvement as documented by bone marrow biopsy, ≥ *5 x 109/L) Platelet count ≥ 50 x 109/L (without a transfusion within 14 days before enrollment) Hemoglobin ≥ 9 g/dL
* Hepatic function, as follows: Aspartate aminotransferase (AST) < *0 x ULN Alanine aminotransferase (ALT) < *0 x ULN Alkaline phosphatase (ALP) < *0 x ULN (< 5 x ULN in subjects whom the PI and sponsor agree that clinical data suggest an extrahepatic source of elevation) Total bilirubin < *5 x ULN (< *0 x ULN for subjects with documented Gilbert's Disease or for whom the indirect bilirubin level suggests an extrahepatic source of elevation) Amylase ≤ *0 x IULN Lipase ≤ *0 x IULN
Exclusion Criteria:
* Primary or disseminated tumor involving the central nervous system (CNS)
* A history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years
* History of allogeneic stem-cell (or other organ) transplantation
* Clinically significant ECG changes which obscure the ability to assess the PR, QT, and QRS interval; congenital long QT syndrome
* QTcF interval > 470 msec
* Active or chronic hepatitis B or hepatitis C infection, determined by serologic tests
* Recent infection requiring intravenous anti-infective treatment that was completed ≤ 14 days before enrollment |