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Safety and Efficacy Study of BMS-908662 Alone or in Combination With Cetuximab in Subjects With K-RAS or B-RAF Mutation Positive Advanced or Metastatic Colorectal Cancer

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: NCT01086267
Recruitment Status : Completed
First Posted : March 15, 2010
Last Update Posted : June 27, 2016
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE March 11, 2010
First Posted Date  ICMJE March 15, 2010
Last Update Posted Date June 27, 2016
Study Start Date  ICMJE July 2010
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2011)
Toxicity will be evaluated according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3 [ Time Frame: Assessments every 1-2 weeks while receiving study drug ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 11, 2010)
Toxicity will be evaluated according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 3 [ Time Frame: Assessments every 1-2 weeks throughout the duration of the trial ]
Change History Complete list of historical versions of study NCT01086267 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2011)
  • Efficacy as determined by estimates of objective response rates and response duration [ Time Frame: Efficacy measured at least every 8 weeks while receiving study drug ]
  • Pharmacodynamics (PD) will be assessed by evaluating markers of RAS/RAF pathway activity [ Time Frame: PD assessed during the first 4 weeks on study ]
  • Pharmacokinetics (PK) for BMS-908662 as determined by minimum observed concentrations [Cmin]. [ Time Frame: PK measured during first 4 weeks on study ]
  • Pharmacokinetics (PK) for BMS-908662 as determined by maximum observed concentrations [Cmax]. [ Time Frame: PK measured during first 4 weeks on study ]
  • Pharmacokinetics (PK) for BMS-908662 as determined by time of maximum observed concentration [Tmax]. [ Time Frame: PK measured during first 4 weeks on study ]
  • Pharmacokinetics (PK) for BMS-908662 as determined by area under the concentration-curve for one dosing interval [AUC(TAU)]. [ Time Frame: PK measured during first 4 weeks on study ]
  • Pharmacokinetics (PK) for BMS-908662 as determined by accumulation index [AI]. [ Time Frame: PK measured during first 4 weeks on study ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2010)
  • Efficacy as determined by estimates of objective response rates and response duration [ Time Frame: Efficacy measured at least every 8 weeks ]
  • Pharmacokinetics for BMS-908662 as determined by minimum and maximum observed concentrations, time of maximum observed concentration, area under the concentration-curve for one dosing interval and the accumulation index [ Time Frame: PK measured during first 4 weeks on study ]
  • Pharmacodynamics will be assessed by evaluating markers of RAS/RAF pathway activity [ Time Frame: PD assessed during the first 4 weeks on study ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of BMS-908662 Alone or in Combination With Cetuximab in Subjects With K-RAS or B-RAF Mutation Positive Advanced or Metastatic Colorectal Cancer
Official Title  ICMJE A Phase 1/2 Study of BMS-908662 (XL281) Alone or in Combination With Cetuximab in Subjects With K-RAS or B-RAF Mutation Positive Advanced or Metastatic Colorectal Cancer
Brief Summary The purpose of the study is to identify a safe and tolerable dose of BMS-908662 in combination with cetuximab; and then to evaluate the tumor response to BMS-908662 when administered alone or in combination with cetuximab
Detailed Description

Phase 1: Single Arm Study

Phase 2: Randomized Controlled, Parallel

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Drug: BMS-908662
    Capsules, Oral, escalating doses starting at 25 mg, every 12 hours (Q 12 h), Continuously
  • Drug: BMS-908662
    Capsules, Oral, (TBD) mg, Q 12 h, Continuously
  • Drug: Cetuximab
    Vial, IV, 400 mg/m² loading dose followed by 250 mg/m² maintenance dose, Weekly, Continuously
Study Arms  ICMJE
  • Experimental: BMS-908662 (A1)
    Phase 1
    Intervention: Drug: BMS-908662
  • Experimental: Cetuximab (A1)
    Phase 1
    Intervention: Drug: Cetuximab
  • Experimental: BMS-908662 (B1)
    Phase 2
    Intervention: Drug: BMS-908662
  • Experimental: BMS-908662 + Cetuximab (B2)
    Phase 2
    Interventions:
    • Drug: BMS-908662
    • Drug: Cetuximab
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: September 29, 2011)
17
Original Estimated Enrollment  ICMJE
 (submitted: March 11, 2010)
121
Actual Study Completion Date  ICMJE August 2011
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects with K-RAS (codon 12 or 13) or B -RAF (V600E) mutation positive advanced or metastatic colorectal cancer who have relapsed or are refractory to 2 or more standard systemic anticancer regimes for metastatic disease, or are intolerant to existing therapies.
  • Histologic or cytologic confirmation of the diagnosis.
  • Eastern Cooperative Oncology Group (ECOG) ≤ 1
  • Adequate organ & marrow function.

Exclusion Criteria:

  • Uncontrolled or significant cardiovascular disease.
  • Phase 2: Prior therapy with a RAF inhibitor.
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 Canada,   United States
Removed Location Countries Belgium
 
Administrative Information
NCT Number  ICMJE NCT01086267
Other Study ID Numbers  ICMJE CA206-001
2010-018944-15 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
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 June 2016

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