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Trial record 3 of 3 for:    BMS-906024

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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01653470
First Posted: July 31, 2012
Last Update Posted: May 17, 2017
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.
Information provided by (Responsible Party):
Bristol-Myers Squibb
  Purpose
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 Intervention Phase
Cancer Drug: Paclitaxel Drug: 5-Fluorouracil (5FU) Drug: Carboplatin Drug: Leucovorin Drug: Irinotecan Drug: BMS-906024 Phase 1

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

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) [ Time Frame: 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 [ 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) ]

Estimated Enrollment: 95
Actual Study Start Date: October 12, 2012
Estimated Study Completion Date: June 15, 2017
Estimated Primary Completion Date: June 14, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Taxol
Drug: BMS-906024
Other Name: 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 Name: Camptosar
Drug: BMS-906024
Other Name: 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 Name: Paraplatin
Drug: Paclitaxel
Other Name: Taxol
Drug: BMS-906024
Other Name: 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 Name: Taxol
Drug: BMS-906024
Other Name: 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 Name: Paraplatin
Drug: Paclitaxel
Other Name: Taxol
Drug: BMS-906024
Other Name: Notch inhibitor

Detailed Description:

DLTs = dose-limiting toxicities

MTD = Maximum tolerated dose

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01653470


Locations
United States, California
Usc/Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Belgium
Local Institution
Brussels, Belgium, 1000
Canada, Alberta
Local Institution
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Local Institution
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Local Institution
Ottawa, Quebec, Canada, K1H 8L6
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01653470     History of Changes
Other Study ID Numbers: CA216-003
2012-003232-23 ( EudraCT Number )
First Submitted: July 18, 2012
First Posted: July 31, 2012
Last Update Posted: May 17, 2017
Last Verified: May 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Paclitaxel
Irinotecan
Camptothecin
Albumin-Bound Paclitaxel
Carboplatin
Fluorouracil
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs