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

January 24, 2020 updated by: Bristol-Myers Squibb

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

DLTs = dose-limiting toxicities

MTD = Maximum tolerated dose

Study Type

Interventional

Enrollment (Actual)

141

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1000
        • Local Institution
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Local Institution
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Local Institution
    • Quebec
      • Ottawa, Quebec, Canada, K1H 8L6
        • Local Institution
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • USC/Norris Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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: Leucovorin
Drug: Irinotecan
Other Names:
  • Camptosar
Drug: BMS-906024
Other Names:
  • Notch inhibitor
Drug: 5-Fluorouracil (5FU)
Other Names:
  • Carac
  • Adrucil
  • Efudex
  • Fluoroplex
  • Efudix
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

What is the study measuring?

Primary Outcome Measures

Outcome 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)
Time Frame: Up to 30 days after the last dose of study medication
Up to 30 days after the last dose of study medication

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
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
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
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
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)
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
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
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
16 time points up to first 3 cycles
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
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
Time Frame: Every 6 weeks until confirmed disease progression, death or discontinuation for other reasons (whichever comes first) [Approximately 24 months]
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)
Baseline (study days -28 to -1)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 12, 2012

Primary Completion (Actual)

May 3, 2017

Study Completion (Actual)

May 8, 2017

Study Registration Dates

First Submitted

July 18, 2012

First Submitted That Met QC Criteria

July 27, 2012

First Posted (Estimate)

July 31, 2012

Study Record Updates

Last Update Posted (Actual)

January 28, 2020

Last Update Submitted That Met QC Criteria

January 24, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA216-003
  • 2012-003232-23 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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