A Phase Ib Ascending Multi-arm, Dose Escalation Study of BMS-906024 Combined With Several Chemotherapy Regimens in Subjects With Advanced or Metastatic Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 141
- 试验地点
- 2
- 主要终点
- 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)
研究概览
简要总结
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
详细描述
DLTs = dose-limiting toxicities
MTD = Maximum tolerated dose
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm B: FOLFIRI (5FU, Leucovorin, Irinotecan) + 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
干预措施: BMS-906024 (Drug)
Arm C: Carboplatin/Paclitaxel + 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
干预措施: Carboplatin (Drug)
Arm A: Paclitaxel + 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
干预措施: Paclitaxel (Drug)
Arm A: Paclitaxel + 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
干预措施: BMS-906024 (Drug)
Arm B: FOLFIRI (5FU, Leucovorin, Irinotecan) + 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
干预措施: 5-Fluorouracil (5FU) (Drug)
Arm B: FOLFIRI (5FU, Leucovorin, Irinotecan) + 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
干预措施: Leucovorin (Drug)
Arm B: FOLFIRI (5FU, Leucovorin, Irinotecan) + 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
干预措施: Irinotecan (Drug)
Arm C: Carboplatin/Paclitaxel + 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
干预措施: Paclitaxel (Drug)
Arm C: Carboplatin/Paclitaxel + 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
干预措施: BMS-906024 (Drug)
Arm D: Paclitaxel + 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
干预措施: Paclitaxel (Drug)
Arm D: Paclitaxel + 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
干预措施: BMS-906024 (Drug)
Arm F: Carboplatin/Paclitaxcel and 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
干预措施: Carboplatin (Drug)
Arm F: Carboplatin/Paclitaxcel and 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
干预措施: Paclitaxel (Drug)
Arm F: Carboplatin/Paclitaxcel and 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
干预措施: BMS-906024 (Drug)
结局指标
主要结局
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)
时间窗: Up to 30 days after the last dose of study medication
次要结局
- 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)
- 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)
- 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)
- 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)
- 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)
- Steady-state infusion concentration (Css) of 5-Fluorouracil (5-FU)(16 time points up to first 3 cycles)
- 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))