Clinical trial NCT01086267: 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: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2010-03-15
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility 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.

Primary outcomes:
measure: Toxicity will be evaluated according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3
timeFrame: Assessments every 1-2 weeks while receiving study drug
Secondary outcomes:
measure: Efficacy as determined by estimates of objective response rates and response duration
timeFrame: Efficacy measured at least every 8 weeks while receiving study drug
measure: Pharmacodynamics (PD) will be assessed by evaluating markers of RAS/RAF pathway activity
timeFrame: PD assessed during the first 4 weeks on study
measure: Pharmacokinetics (PK) for BMS-908662 as determined by minimum observed concentrations [Cmin].
timeFrame: PK measured during first 4 weeks on study
measure: Pharmacokinetics (PK) for BMS-908662 as determined by maximum observed concentrations [Cmax].
timeFrame: PK measured during first 4 weeks on study
measure: Pharmacokinetics (PK) for BMS-908662 as determined by time of maximum observed concentration [Tmax].
timeFrame: PK measured during first 4 weeks on study
measure: Pharmacokinetics (PK) for BMS-908662 as determined by area under the concentration-curve for one dosing interval [AUC(TAU)].
timeFrame: PK measured during first 4 weeks on study
measure: Pharmacokinetics (PK) for BMS-908662 as determined by accumulation index [AI].
timeFrame: PK measured during first 4 weeks on study
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Oncology Research Associates D/B/A
state: Arizona
city: Los Angeles
country: United States
facility: Usc Norris Comprehensive Cancer Center
state: California
city: Ottawa
country: Canada
facility: Local Institution
state: Ontario
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: