Sorafenib and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer
This phase II trial is studying how well giving sorafenib together with bevacizumab works in treating patients with metastatic colorectal cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with bevacizumab may kill more tumor cells
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Drug: sorafenib tosylate
Other: diagnostic laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Sorafenib/Avastin® as Salvage Therapy in Patients With Metastatic Colorectal Cancer|
- Progression-free survival rate [ Time Frame: At 3 months ] [ Designated as safety issue: No ]The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
- Response rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Confidence intervals for the response rate will be calculated according to the approach of Duffy and Santner. Simple frequency analysis will be conducted to see if response rate is related to prior treatment and the selected tumor biomarkers. Descriptive statistics will be used to investigate how prior treatment affects various other measures as well.
- Overall survival [ Time Frame: Time from registration to death, assessed up to 2 years ] [ Designated as safety issue: No ]The distribution of overall survival will be estimated using Kaplan-Meier methodology.
- Safety of study treatment [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]Will be summarized by placing adverse events responses in tabular form. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until June 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning July 1, 2011.
- Feasibility of study treatment [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Will be evaluated based on the number of patients who are able to tolerate the regimen, how long they tolerate it and whether they elect to stop treatment.
|Study Start Date:||September 2009|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (sorafenib tosylate and bevacizumab)
Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies
Drug: sorafenib tosylate
Other Names:Other: diagnostic laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesBiological: bevacizumab
I. Evaluate proportion of patients who are progression-free at 3 months (in historic comparison with results for single-agent bevacizumab in ECOG 3200).
I. Response rate (RR) II. Overall survival (OS) III. Safety IV. Feasibility
I. To determine the relationship between tumor biomarkers and circulating biomarkers of vascular response and clinical outcome in metastatic colorectal cancer patients treated with the sorafenib/bevacizumab combination.
II. As part of ongoing research for NCCTG GI studies, we are banking leftover tissue and blood products (i.e., plasma, DNA, and buffy coat) for future studies.
OUTLINE: This is a multicenter study.
Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies.
After completion of study treatment, patients are followed up periodically for up to 2 years.