Advanced cancer MedDRA version: 9.1 Level: LLT Classification code 10048683 Term: Advanced cancer
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase 1: 1) Signed Written Informed Consent a) The signed informed consent form. 2) Target population a) Histologically or cytologically confirmed diagnosis of solid tumor malignancy which has progressed on standard therapy or for whom no standard therapy is known; i) Minimum availability of 10 archived tumor tissue slides, or subject’s willingness and ability to undergo tumor biopsy collection for IHC analysis; either available within 28 days or greater from Cycle 1 Day 1; b) Measurable or non-measurable disease as defined by RECIST criteria; c) Adequate recovery from recent surgery and radiation therapy. At least one week must have elapsed from the time of a minor surgery and at least 3 weeks for major surgery and radiation therapy; d) Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Protocol Appendix 3); e) Available for treatment and follow-up. Subjects enrolled in this trial must be treated at the participating center; f) At least four weeks must have elapsed from the last dose of carboplatin, immunotherapy or chemotherapy, (six weeks for nitrosoureas, or mitomycin C), prior to beginning protocol therapy. Hormonal anti-cancer agents and nontraditional cytotoxic agents, such as trastuzumab, gefitinib, erlotinib, cetuximab, bevacizumab, are not considered chemotherapy regimens when administered alone, and at least 4 weeks must have elapsed from the last dose of this class of agents before study drug administration. Subjects must have recovered to baseline or Grade 1 from the toxicities resulting from previous therapies. 3) Age and Sex a) Men and women, ages 18 and greater; Phase 2 includes the above inclusion criteria and the following: Subjects with measurable, confirmed, advanced ovarian (including primary peritoneal or fallopian tube), renal cell or breast cancer or non-measurable, confirmed, advanced ovarian (including primary peritoneal or fallopian tube) cancer with CA125 = 2x ULN, which has progressed on standard therapy or for whom no standard therapy is known, in place of: - Histologically or cytologically confirmed diagnosis of solid tumor malignancy which has progressed on standard therapy or for whom no standard therapy is known. • IHC will be utilized to select subjects prospectively for assignment to the FR+ and FR- groups. • For subjects with renal cell cancer, up to 3 prior treatment regimens are permitted, and for subjects with ovarian cancer up to 4 prior treatment regimens are permitted. For subjects with breast cancer, up to 4 prior cytotoxic treatment regimens, with no more than 3 in the advanced disease setting, are permitted. Hormonal therapies are not included in these counts of previous treatment regimens. - If a treatment is stopped and restarted after a disease recurrence, that will be counted as 2 regimens. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Phase 1 1) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period as per the Investigator’s discretion to avoid pregnancy throughout the study and for up to 4 weeks after the study in such a manner that the risk of pregnancy is minimized. b) WOCBP using a contraceptive method deemed inappropriate by the Investigator. c) Women who are pregnant or breastfeeding Phase 1 1) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period as per the Investigator’s discretion to avoid pregnancy throughout the study and for up to 4 weeks after the study in such a manner that the risk of pregnancy is minimized. b) WOCBP using a contraceptive method deemed inappropriate by the Investigator. c) Women who are pregnant or breastfeeding on thyroid replacement therapy and whose symptoms of thyroiditis are resolved to = Grade 1 before enrollment are eligible; i) Any other sound medical, psychiatric and/or social reason as determined by the Investigator. 3) Physical and Laboratory Test Findings a) Inadequate hematologic function with absolute neutrophils <1,500/mm3, platelets <100,000/mm3, or hemoglobin <10 g/dL; b) Inadequate hepatic function with serum bilirubin =1.5 times the upper institutional limits of normal, ALT = 2.5 times the upper institutional limits of normal, AST = 2.5 times the upper institutional limits of normal; c) Inadequate renal function defined as a calculated creatinine clearance of < 60 mL/min according to the Cockcroft-Gault formula: i) In men: [eGFRCG(mL/min)]=(140 - age) x weight (kg) / (72 x serum creatinine concentration in mg/dL) ii) In women, multiply this result by 0.85 d) Inadequate thyroid function with free T4 and/or TSH outside of the institutional limits of normal unless approved by Medical Monitor. 4) Allergies and Adverse Drug Reactions a) History of any significant drug allergy which in the Investigator’s discretion would inhibit the subject’s participation. 5) Prohibited Treatments and/or Therapies a) Exposure to any investigational drug or placebo within 4 weeks of study drug administration; b) Use of multi-vitamins and/or folic acid supplements for 1 week prior to Cycle 1 Day 1 and throughout the course of the trial; c) Other concurrent chemotherapy hormonal therapy, immunotherapy regimens or radiation therapy, standard or investigational; d) Prior radiation must not have included =25% of major bone marrow containing areas (pelvis, lumbar spine); e) Use of steroids except in the following instances, in which the use of steroids is allowed: • for anti-emetic purposes. • continuing therapy for controlled brain metastases. • chronic steroid use in the context of a disease requiring such use . • for appetite stimulation. • Treatment of a hypersensitivity reaction and as subsequent premedication for the prevention of same • Premedication prior to CT scan requiring IV contrast dye in subjects with IV contrast dye allergy • Other uses of steroids may be allowed with prior approval from the Medical Monitor f) The use of known P-gp-inhibitors (Prot. App. 8) is prohibited for 1 week prior to Cycle 1 Day 1 and throughout the course of the trial. 6) Other a) Inability to provide an archived tumor sample (10 slides) for analysis within 28 days of study drug administration; b) Prisoners or involuntarily incarcerated subjects; c) Subjects who are compulsorily detaine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 Primary Objective: • To determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and recommended Phase 2 dose of BMS-753493 administered as a 3 to 5 minute bolus i.v. infusion on Days 1 through 4 of a 21-day cycle in subjects with confirmed solid tumor malignancy. Phase 2 Primary Objective: • To assess efficacy of BMS-753493 in subjects with advanced ovarian, renal or breast cancer as measured by the tumor response rate according to RECIST criteria or CA125 levels.;Secondary Objective: Phase 1 Secondary Objectives: • To describe the overall safety profile of BMS-753493 administered as a 3 to 5 minute bolus i.v. infusion on Days 1 through 4 of a 21-day cycle; • To assess the PK of BMS-753493 and BMS-748285; • To evaluate the impact of BMS-753493 and BMS-748285 on QTcF; • To describe any preliminary evidence of anti-tumor activity of BMS-753493 for all treated subjects. Phase 2 Secondary Objectives: • To describe any association between anti-tumor activity and FR status as assessed by IHC; • To further characterize safety and tolerability of BMS-753493 in subjects with advanced ovarian, renal or breast cancer; • To assess the response duration and progression-free survival (PFS); • To evaluate the impact of BMS-753493 and BMS-748285 on QTcF; • To assess the PK of BMS-753493 and BMS-748285.;Primary end point(s): • Safety Outcome Measures: All subjects who receive BMS-753493 will be evaluated for safety. Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, clinical laboratory tests, electrocardiograms, pulmonary function tests, and multigated radionuclide angiography (MUGA) scans or echocardiograms. Toxicity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. ECG assessments will be collected at screening (single ECG) pre-dose (triplicate ECGs) a | — |
Countries
United Kingdom
Outcome results
None listed