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

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

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

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: BMS-908662; Drug: BMS-908662; Drug: Cetuximab

Detailed Description

Phase 1: Single Arm Study

Phase 2: Randomized Controlled, Parallel

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 1C3
      • Local Institution
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Oncology Research Associates D/B/A
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMS-908662 (A1); Phase 1	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
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, escalating doses starting at 25 mg, every 12 hours (Q 12 h), Continuously; Drug: BMS-908662; Capsules, Oral, (TBD) mg, Q 12 h, Continuously
Experimental: BMS-908662 + Cetuximab (B2); Phase 2	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Toxicity will be evaluated according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3	Assessments every 1-2 weeks while receiving study drug

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy as determined by estimates of objective response rates and response duration	Efficacy measured at least every 8 weeks while receiving study drug
Pharmacodynamics (PD) will be assessed by evaluating markers of RAS/RAF pathway activity	PD assessed during the first 4 weeks on study
Pharmacokinetics (PK) for BMS-908662 as determined by minimum observed concentrations [Cmin].	PK measured during first 4 weeks on study
Pharmacokinetics (PK) for BMS-908662 as determined by maximum observed concentrations [Cmax].	PK measured during first 4 weeks on study
Pharmacokinetics (PK) for BMS-908662 as determined by time of maximum observed concentration [Tmax].	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)].	PK measured during first 4 weeks on study
Pharmacokinetics (PK) for BMS-908662 as determined by accumulation index [AI].	PK measured during first 4 weeks on study

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: March 11, 2010
• First Submitted That Met QC Criteria: March 11, 2010
• First Posted (Estimate): March 15, 2010

Study Record Updates

• Last Update Posted (Estimate): June 27, 2016
• Last Update Submitted That Met QC Criteria: June 23, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: CA206-001; 2010-018944-15 (EudraCT Number)