Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01653470
Recruitment Status : Completed
First Posted : July 31, 2012
Last Update Posted : January 28, 2020
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE July 18, 2012
First Posted Date  ICMJE July 31, 2012
Last Update Posted Date January 28, 2020
Actual Study Start Date  ICMJE October 12, 2012
Actual Primary Completion Date May 3, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2012)
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) [ Time Frame: Up to 30 days after the last dose of study medication ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2012)
  • 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline (study days -28 to -1) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE A Phase Ib Ascending Multi-arm, Dose Escalation Study of BMS-906024 Combined With Several Chemotherapy Regimens in Subjects With Advanced or Metastatic Tumors
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE
  • Drug: Paclitaxel
    Other Name: Taxol
  • Drug: 5-Fluorouracil (5FU)
    Other Names:
    • Adrucil
    • Carac
    • Efudix
    • Efudex
    • Fluoroplex
  • Drug: Carboplatin
    Other Name: Paraplatin
  • Drug: Leucovorin
  • Drug: Irinotecan
    Other Name: Camptosar
  • Drug: BMS-906024
    Other Name: Notch inhibitor
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Paclitaxel
    • Drug: BMS-906024
  • 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
    Interventions:
    • Drug: 5-Fluorouracil (5FU)
    • Drug: Leucovorin
    • Drug: Irinotecan
    • Drug: BMS-906024
  • 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
    Interventions:
    • Drug: Carboplatin
    • Drug: Paclitaxel
    • Drug: BMS-906024
  • 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
    Interventions:
    • Drug: Paclitaxel
    • Drug: BMS-906024
  • 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
    Interventions:
    • Drug: Carboplatin
    • Drug: Paclitaxel
    • Drug: BMS-906024
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 15, 2017)
141
Original Estimated Enrollment  ICMJE
 (submitted: July 27, 2012)
60
Actual Study Completion Date  ICMJE May 8, 2017
Actual Primary Completion Date May 3, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01653470
Other Study ID Numbers  ICMJE CA216-003
2012-003232-23 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP