Cancer
Conditions
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
Interventions
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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) | — |
| 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 |
Countries
Belgium, Canada, United States
Outcome results
None listed