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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 currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01653470
First received: July 18, 2012
Last updated: June 12, 2014
Last verified: May 2014
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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] ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Estimated Enrollment: 95
Study Start Date: October 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01653470

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

Locations
United States, California
Usc/Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Anthony El-Khoueiry, Site 001         
Belgium
Local Institution Recruiting
Brussels, Belgium, 1000
Contact: Site 0005         
Canada, Alberta
Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Siu-Chung Chu, Site 0003    780-577-8137      
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Lillian L Siu, Site 0002    416-946-4501 ext 3450      
Canada, Quebec
The Ottawa Hospital Cancer Centre Recruiting
Ottawa, Quebec, Canada, K1H 8L6
Contact: Glenwood Goss, Site 0004    613-737-7700 ext 70300      
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01653470     History of Changes
Other Study ID Numbers: CA216-003, 2012-003232-23
Study First Received: July 18, 2012
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Hungary: National Institute of Pharmacy

Additional relevant MeSH terms:
Carboplatin
Fluorouracil
Irinotecan
Paclitaxel
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014