Colorectal Cancer
Conditions
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
Interventions
DRUGBMS-908662
Capsules, Oral, escalating doses starting at 25 mg, every 12 hours (Q 12 h), Continuously
DRUGCetuximab
Vial, IV, 400 mg/m² loading dose followed by 250 mg/m² maintenance dose, Weekly, Continuously
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Efficacy as determined by estimates of objective response rates and response duration | Efficacy measured at least every 8 weeks while receiving study drug |
| 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 |
| Pharmacokinetics (PK) for BMS-908662 as determined by time of maximum observed concentration [Tmax]. | PK measured during first 4 weeks on study |
Countries
Canada, United States
Outcome results
None listed