Clinical trial NCT01653470: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-07-31
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: Up to 30 days after the last dose of study medication
Secondary outcomes:
measure: 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
timeFrame: 16 time points up to first 3 cycles
measure: 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
timeFrame: 16 time points up to first 3 cycles
measure: 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
timeFrame: 16 time points up to first 3 cycles
measure: 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)
timeFrame: 16 time points up to first 3 cycles
measure: 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
timeFrame: 16 time points up to first 3 cycles
measure: Steady-state infusion concentration (Css) of 5-Fluorouracil (5-FU)
timeFrame: 16 time points up to first 3 cycles
measure: 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
timeFrame: Every 6 weeks until confirmed disease progression, death or discontinuation for other reasons (whichever comes first) [Approximately 24 months]
measure: 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
timeFrame: Baseline (study days -28 to -1)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc/Norris Comprehensive Cancer Center
state: California
city: Brussels
country: Belgium
facility: Local Institution
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Ottawa
country: Canada
facility: Local Institution
state: Quebec
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: