Phase I/II Study of Capecitabine Plus Aflibercept to Treat Metastatic Colorectal Cancer (X-TRAP)
The Primary Phase I objectives are to determine the recommended phase II dose for the capecitabine and aflibercept doublet combination; and to describe any dose limiting and non-dose limiting toxicities. The Phase II Primary objective is to determine progression free survival associated with this regimen. The Phase II secondary objectives are to determine response rate associated with this regimen; to determine overall survival associated with this regimen; and to explore any correlation of clinical outcome with baseline and on treatment changes in blood-based angiogenesis biomarkers.
This open-label, non-randomized phase I/II trial is designed to assess the safety, tolerability and RPTD of capecitabine plus aflibercept in adult subjects with metastatic colorectal cancer.
Metastatic Colorectal Cancer
Drug: Capecitabine and aflibercept
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||X-TRAP: Phase I/II Study of Capecitabine Plus Aflibercept in Metastatic Colorectal Cancer|
- Recommended Phase II dose (RPTD) for the capecitabine and aflibercept doublet combination [ Time Frame: RPTD for the study will be determined at the completion of Phase I; up to 1 year ] [ Designated as safety issue: Yes ]Phase 1 of this study will be the dose escalation component to determine safety and the RPTD for the capecitabine plus aflibercept combination. Dose escalation will begin with cohort 1 and continue as described in the protocol. RPTD is determined by the dose limiting and non-dose limiting toxicities (Primary obj 2 for Phase I)
- Progression free survival associated with the regimen [ Time Frame: 2 months progression free ] [ Designated as safety issue: No ]The primary objective of Phase II is to describe any signs of clinical activity, including response rate and progression free survival in patients with metastatic colorectal cancer. For the purpose of sample size determination, a patient will be considered to have been successfully treated if the patient remained progression-free 2 months after the administration of the experimental treatment.
- Frequency of best response [ Time Frame: approximately every 9 weeks and/or restaging ] [ Designated as safety issue: No ]Response is assessed at restaging, approximately every 9 weeks. For response, the frequency of best response (CR+PR) to the treatment will be tabulated and its 95% confidence intervals will be computed.
- Overall survival [ Time Frame: Subjects will be followed until death which is estimated to be on average 6 months - 1 year after coming off protocol therapy ] [ Designated as safety issue: No ]Overall survival associated with this regimen will be assessed. Subjects will be followed until death which is estimated to be on average 6 months - 1 year after coming off protocol therapy.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||August 2017|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
|Experimental: Capecitabine and Aflibercept||
Drug: Capecitabine and aflibercept
A standard 3+3 dose escalation format will be used. Since each agent is well tolerated as monotherapy and in combination with other chemotherapy regimens, we will start at capecitabine 850mg/m2 to be given days 1-14 and off days 15-21. The dose will then be escalated to 1000mg/m2, given on the same schedule. The dose of aflibercept will be held constant at 6 mg/kg, given intravenously every 3 weeks. Both agents will be administered on a 21-day cycle. Once the RPTD of the doublet combination has been identified, an additional 50 subjects with metastatic colorectal cancer will be added to a single-arm, Phase II portion for expanded safety, response and biomarker data.
|Contact: Brant Hamel, PhDfirstname.lastname@example.org|
|Contact: Anthony Amara, MSWemail@example.com|
|United States, North Carolina|
|Duke Cancer Center, Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Principal Investigator: Fatima A Rangwala, MD, PhD|
|Principal Investigator:||Fatima A Rangwala, MD, PhD||Duke University|