Study to Evaluate Safety & Tolerability of BMS-906024 in Combination With Chemotherapy & to Define DLTs & MTD of BMS-906024 in Combination With One of the Following Chemotherapy Regimens; Weekly Paclitaxel, 5FU+Irinotecan or Carboplatin+Paclitaxel in Subjects With Advanced / Metastatic Solid Tumors
Phase 1
Completed
- Conditions
- Cancer
- Interventions
- Registration Number
- NCT01653470
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to identify a safe and tolerable dose of BMS-906024 in combination with each of the following three chemotherapy regimens: Paclitaxel, 5FU plus Irinotecan (FOLFIRI), or Carboplatin plus Paclitaxel in subjects with advanced or metastatic solid tumors
- Detailed Description
DLTs = dose-limiting toxicities
MTD = Maximum tolerated dose
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 141
Inclusion Criteria
- Subjects with advanced or metastatic solid tumors for whom a chemotherapy regimen is considered appropriate
- Subjects with non-small cell lung cancer and triple-negative breast cancer are preferred
- Biopsy accessible tumor (may use archived tumor samples under certain circumstances)
- Life expectancy of at least 3 months
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
- Measurable disease
Exclusion Criteria
- Uncontrolled brain metastases
- Infection
- Gastrointestinal (GI) disease with increased risk of diarrhea (e.g. inflammatory bowel disease)
- Uncontrolled or significant cardiovascular disease
- Subjects taking medications known to increase risk of Torsades de Pointes
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: FOLFIRI (5FU, Leucovorin, Irinotecan) + BMS-906024 BMS-906024 5FU Bolus 400 mg/m2, 5FU Infusion 2400 mg/m2, Irinotecan 180 mg/m2 solution, Leucovorin 400 mg/m2 solution intravenously once every 2 weeks and BMS- 906024 4 mg or 6 mg solution intravenously once weekly continuously until disease progression or unacceptable toxicity Arm D: Paclitaxel + BMS-906024 BMS-906024 Paclitaxel 80 mg/m2 solution once weekly and BMS-906024 4 mg or 6 mg solution once every 2 weeks intravenously continuously until disease progression or unacceptable toxicity Arm C: Carboplatin/Paclitaxel + BMS-906024 BMS-906024 Carboplatin AUC 6 / Paclitaxel 200 mg/m2 solution once every 3 weeks and BMS-906024 4 mg or 6 mg solution once weekly intravenously continuously until disease progression or unacceptable toxicity Arm A: Paclitaxel + BMS-906024 BMS-906024 Paclitaxel 80 mg/m2 solution and BMS-906024 4 mg or 6 mg solution intravenously once weekly continuously until disease progression or unacceptable toxicity Arm B: FOLFIRI (5FU, Leucovorin, Irinotecan) + BMS-906024 5-Fluorouracil (5FU) 5FU Bolus 400 mg/m2, 5FU Infusion 2400 mg/m2, Irinotecan 180 mg/m2 solution, Leucovorin 400 mg/m2 solution intravenously once every 2 weeks and BMS- 906024 4 mg or 6 mg solution intravenously once weekly continuously until disease progression or unacceptable toxicity Arm B: FOLFIRI (5FU, Leucovorin, Irinotecan) + BMS-906024 Irinotecan 5FU Bolus 400 mg/m2, 5FU Infusion 2400 mg/m2, Irinotecan 180 mg/m2 solution, Leucovorin 400 mg/m2 solution intravenously once every 2 weeks and BMS- 906024 4 mg or 6 mg solution intravenously once weekly continuously until disease progression or unacceptable toxicity Arm F: Carboplatin/Paclitaxcel and BMS-906024 BMS-906024 Carboplatin AUC 6 / Paclitaxel 200 mg/m2 solution once every 3 weeks and BMS-906024 4 mg or 6 mg solution once every 3 weeks intravenously continuously until disease progression or unacceptable toxicity Arm A: Paclitaxel + BMS-906024 Paclitaxel Paclitaxel 80 mg/m2 solution and BMS-906024 4 mg or 6 mg solution intravenously once weekly continuously until disease progression or unacceptable toxicity Arm B: FOLFIRI (5FU, Leucovorin, Irinotecan) + BMS-906024 Leucovorin 5FU Bolus 400 mg/m2, 5FU Infusion 2400 mg/m2, Irinotecan 180 mg/m2 solution, Leucovorin 400 mg/m2 solution intravenously once every 2 weeks and BMS- 906024 4 mg or 6 mg solution intravenously once weekly continuously until disease progression or unacceptable toxicity Arm C: Carboplatin/Paclitaxel + BMS-906024 Carboplatin Carboplatin AUC 6 / Paclitaxel 200 mg/m2 solution once every 3 weeks and BMS-906024 4 mg or 6 mg solution once weekly intravenously continuously until disease progression or unacceptable toxicity Arm C: Carboplatin/Paclitaxel + BMS-906024 Paclitaxel Carboplatin AUC 6 / Paclitaxel 200 mg/m2 solution once every 3 weeks and BMS-906024 4 mg or 6 mg solution once weekly intravenously continuously until disease progression or unacceptable toxicity Arm D: Paclitaxel + BMS-906024 Paclitaxel Paclitaxel 80 mg/m2 solution once weekly and BMS-906024 4 mg or 6 mg solution once every 2 weeks intravenously continuously until disease progression or unacceptable toxicity Arm F: Carboplatin/Paclitaxcel and BMS-906024 Paclitaxel Carboplatin AUC 6 / Paclitaxel 200 mg/m2 solution once every 3 weeks and BMS-906024 4 mg or 6 mg solution once every 3 weeks intravenously continuously until disease progression or unacceptable toxicity Arm F: Carboplatin/Paclitaxcel and BMS-906024 Carboplatin Carboplatin AUC 6 / Paclitaxel 200 mg/m2 solution once every 3 weeks and BMS-906024 4 mg or 6 mg solution once every 3 weeks intravenously continuously until disease progression or unacceptable toxicity
- Primary Outcome Measures
Name Time Method Safety assessment based on reports of adverse events and clinical laboratory tests as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Up to 30 days after the last dose of study medication
- Secondary Outcome Measures
Name Time Method Maximum observed plasma concentration (Cmax) of BMS-906024 and BMS-911557 (the active metabolite of BMS-906024), Paclitaxel, Irinotecan, SN-38 (the active metabolite of Irinotecan) and Carboplatin 16 time points up to first 3 cycles Duration of first 3 cycles for Arm A: 10 weeks; Arm B: 6 weeks; Arm C: 9 weeks
Trough observed plasma concentration (Cmin) of BMS-906024 and BMS-911557 (the active metabolite of BMS-906024), Paclitaxel, Irinotecan, SN-38 (the active metabolite of Irinotecan) and Carboplatin 16 time points up to first 3 cycles Duration of first 3 cycles for Arm A: 10 weeks; Arm B: 6 weeks; Arm C: 9 weeks
Time of maximum observed plasma concentration (Tmax) of BMS-906024 and BMS-911557 (the active metabolite of BMS-906024), Paclitaxel, Irinotecan, SN-38 (the active metabolite of Irinotecan) and Carboplatin 16 time points up to first 3 cycles Duration of first 3 cycles for Arm A: 10 weeks; Arm B: 6 weeks; Arm C: 9 weeks
Area under the concentration-time curve during a dosing interval of tau [AUC(TAU)] of BMS-906024 and BMS-911557 (the active metabolite of BMS-906024) 16 time points up to first 3 cycles Duration of first 3 cycles for Arm A: 10 weeks; Arm B: 6 weeks; Arm C: 9 weeks
Area under the concentration-time curve from time 0 to the time of the last sample collected in the dosing interval [AUC(0-T)] of Paclitaxel, Irinotecan, SN-38 (the active metabolite of Irinotecan) and Carboplatin 16 time points up to first 3 cycles Duration of first 3 cycles for Arm A: 10 weeks; Arm B: 6 weeks; Arm C: 9 weeks
Steady-state infusion concentration (Css) of 5-Fluorouracil (5-FU) 16 time points up to first 3 cycles Duration of first 3 cycles for Arm A: 10 weeks; Arm B: 6 weeks; Arm C: 9 weeks
Tumor response [as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (v.1.1) criteria], best overall response (BOR), duration of response, and progression free survival (PFS) will be assessed Every 6 weeks until confirmed disease progression, death or discontinuation for other reasons (whichever comes first) [Approximately 24 months] Gene mutation status of Notch activation markers as well as other genes of interest in relevant indications, in tumor, and gene expression levels of Notch activation markers, such as but not limited to Hes1, Deltex1, in tumor Baseline (study days -28 to -1)
Trial Locations
- Locations (2)
Usc/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Local Institution
🇨🇦Ottawa, Quebec, Canada