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

Sponsor

Bristol-Myers Squibb (Industry)

Overall Status

Completed

CT.gov ID

NCT01653470

Collaborator

(none)

141

Enrollment

Locations

Arms

54.8

Actual Duration (Months)

28.2

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: Paclitaxel Drug: 5-Fluorouracil (5FU) Drug: Carboplatin Drug: Leucovorin Drug: Irinotecan Drug: Paclitaxel Drug: BMS-906024	Phase 1

Detailed Description

DLTs = dose-limiting toxicities

MTD = Maximum tolerated dose

Study Design

Study Type:

Interventional

Actual Enrollment :

141 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ib Ascending Multi-arm, Dose Escalation Study of BMS-906024 Combined With Several Chemotherapy Regimens in Subjects With Advanced or Metastatic Tumors

Actual Study Start Date :

Oct 12, 2012

Actual Primary Completion Date :

May 3, 2017

Actual Study Completion Date :

May 8, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Paclitaxel Other Names: Taxol Drug: BMS-906024 Other Names: Notch inhibitor
Experimental: 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	Drug: 5-Fluorouracil (5FU) Other Names: Adrucil Carac Efudix Efudex Fluoroplex Drug: Leucovorin Drug: Irinotecan Other Names: Camptosar Drug: BMS-906024 Other Names: Notch inhibitor
Experimental: 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	Drug: Carboplatin Other Names: Paraplatin Drug: Paclitaxel Other Names: Taxol Drug: BMS-906024 Other Names: Notch inhibitor
Experimental: 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	Drug: Paclitaxel Other Names: Taxol Drug: BMS-906024 Other Names: Notch inhibitor
Experimental: 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	Drug: Carboplatin Other Names: Paraplatin Drug: Paclitaxel Other Names: Taxol Drug: BMS-906024 Other Names: Notch inhibitor

Outcome Measures

Primary Outcome Measures

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

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Usc/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	Local Institution	Brussels		Belgium	1000
3	Local Institution	Edmonton	Alberta	Canada	T6G 1Z2
4	Local Institution	Toronto	Ontario	Canada	M5G 2M9
5	Local Institution	Ottawa	Quebec	Canada	K1H 8L6