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

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01086267
First received: March 11, 2010
Last updated: November 29, 2011
Last verified: March 2011
  Purpose

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


Condition Intervention Phase
Colorectal Cancer
Drug: BMS-908662
Drug: Cetuximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Pharmacodynamics (PD) will be assessed by evaluating markers of RAS/RAF pathway activity [ Time Frame: PD assessed during the first 4 weeks on study ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK) for BMS-908662 as determined by minimum observed concentrations [Cmin]. [ Time Frame: PK measured during first 4 weeks on study ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK) for BMS-908662 as determined by maximum observed concentrations [Cmax]. [ Time Frame: PK measured during first 4 weeks on study ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK) for BMS-908662 as determined by time of maximum observed concentration [Tmax]. [ Time Frame: PK measured during first 4 weeks on study ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK) for BMS-908662 as determined by accumulation index [AI]. [ Time Frame: PK measured during first 4 weeks on study ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: July 2010
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMS-908662 (A1)
Phase 1
Drug: BMS-908662
Capsules, Oral, escalating doses starting at 25 mg, every 12 hours (Q 12 h), Continuously
Experimental: Cetuximab (A1)
Phase 1
Drug: Cetuximab
Vial, IV, 400 mg/m² loading dose followed by 250 mg/m² maintenance dose, Weekly, Continuously
Experimental: BMS-908662 (B1)
Phase 2
Drug: BMS-908662
Capsules, Oral, (TBD) mg, Q 12 h, Continuously
Experimental: BMS-908662 + Cetuximab (B2)
Phase 2
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

Detailed Description:

Phase 1: Single Arm Study

Phase 2: Randomized Controlled, Parallel

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01086267

Locations
United States, Arizona
Oncology Research Associates D/B/A
Scottsdale, Arizona, United States, 85258
United States, California
Usc Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Canada, Ontario
Local Institution
Ottawa, Ontario, Canada, K1H 1C3
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01086267     History of Changes
Other Study ID Numbers: CA206-001, 2010-018944-15
Study First Received: March 11, 2010
Last Updated: November 29, 2011
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Belgium: Ministry of Social Affairs, Public Health and the Environment
Korea: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014