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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01086267
• Other study ID #: CA206-001
• Secondary ID: 2010-018944-15
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 11, 2010
• Last updated: June 23, 2016
• Start date: July 2010
• Est. completion date: August 2011

Study information

• Verified date: June 2016
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaBelgium: Ministry of Social Affairs, Public Health and the EnvironmentKorea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Description:

Phase 1: Single Arm Study

Phase 2: Randomized Controlled, Parallel

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• BMS-908662
Capsules, Oral, escalating doses starting at 25 mg, every 12 hours (Q 12 h), Continuously
• BMS-908662
Capsules, Oral, (TBD) mg, Q 12 h, Continuously
• Cetuximab
Vial, IV, 400 mg/m² loading dose followed by 250 mg/m² maintenance dose, Weekly, Continuously

Locations

Country	Name	City	State
Canada	Local Institution	Ottawa	Ontario
United States	Usc Norris Comprehensive Cancer Center	Los Angeles	California
United States	Oncology Research Associates D/B/A	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Efficacy as determined by estimates of objective response rates and response duration		Efficacy measured at least every 8 weeks while receiving study drug	No
Secondary	Pharmacodynamics (PD) will be assessed by evaluating markers of RAS/RAF pathway activity		PD assessed during the first 4 weeks on study	No
Secondary	Pharmacokinetics (PK) for BMS-908662 as determined by minimum observed concentrations [Cmin].		PK measured during first 4 weeks on study	No
Secondary	Pharmacokinetics (PK) for BMS-908662 as determined by maximum observed concentrations [Cmax].		PK measured during first 4 weeks on study	No
Secondary	Pharmacokinetics (PK) for BMS-908662 as determined by time of maximum observed concentration [Tmax].		PK measured during first 4 weeks on study	No
Secondary	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	No
Secondary	Pharmacokinetics (PK) for BMS-908662 as determined by accumulation index [AI].		PK measured during first 4 weeks on study	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form