Sorafenib in Treating Patients With Malignant Gastrointestinal Stromal Tumor That Progressed During or After Previous Treatment With Imatinib Mesylate and Sunitinib Malate
This phase II trial is studying how well sorafenib works in treating patients with malignant gastrointestinal stromal tumor that progressed during or after previous treatment with imatinib mesylate and sunitinib malate. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of BAY 43-9006 for Imatinib- and Sunitinib-Resistant Malignant Gastrointestinal Stromal Tumor|
- Objective response rate (partial response [PR] or complete response [CR]) [ Time Frame: Computed Tomography (CT) scans for disease reassessment will be obtained pre-therapy and every 8 weeks. In addition to a baseline scan, confirmatory scans will also be obtained 4 weeks following initial documentation of objective response. ] [ Designated as safety issue: No ]Objective response will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria from the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is documented. CR is the disappearance of all target lesions. PR requires at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A 5% response rate precludes further study whereas a 20% response rate would indicate that further investigation of the treatment is warranted.
- Toxicity [ Time Frame: Evaluated every 8 weeks ] [ Designated as safety issue: Yes ]All toxicities will be graded using the Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3), except for hypertension and rash. Minor changes from the CTCAE guidelines for hypertension and rash are based on observations in other trials and the frequency of monitoring in this protocol.
- Progression-free survival (time to disease progression or death) as assessed using standard Kaplan-Meier methods [ Time Frame: CT scans for disease reassessment will be obtained pre-therapy and every 8 weeks. In addition to a baseline scan, confirmatory scans will also be obtained 4 weeks following initial documentation of objective response. ] [ Designated as safety issue: No ]Progression-free survival will be documented according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (e.g. there is a new lesion or there is 20% increase in unidimensional tumor size) from the start of treatment.
- Overall survival as assessed using standard Kaplan-Meier methods [ Time Frame: Unspecified ] [ Designated as safety issue: No ]Median overall survival and progression-free survival times will be estimated and confidence intervals generated using the method described in Brookmeyer and Crowley (1982).
- Mutational status of KIT and PDGFA [ Time Frame: Tumor specimens will be collected pre-therapy (at time of patient enrollment) for DNA extraction. If patient specimens are available following treatment with imatinib, these will be analyzed as well. ] [ Designated as safety issue: No ]Known sites of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) mutations will be analyzed for correlation with response to drug. Mutational status will be correlated with outcomes by using Fisher's exact test to compare the frequency of responses in patients with and without specific mutations. These comparisons will have relatively low power and we will look for trends only. A Cox regression model will also be fit to determine whether there appears to be any association between mutational status and time to disease progression or death.
|Study Start Date:||September 2005|
|Primary Completion Date:||February 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (sorafenib tosylate)
Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: sorafenib tosylate
I. To determine the objective response rate of patients with imatinib and sunitinib-resistant malignant gastrointestinal stromal tumor who are treated with BAY 43-9006.
I. To determine the toxicity experienced by patients with imatinib and sunitinib -resistant malignant gastrointestinal stromal tumor who are treated with BAY 43-9006.
II. To determine progression-free survival and overall survival in patients with imatinib and sunitinib -resistant malignant gastrointestinal stromal tumor who are treated with BAY 43-9006.
I. To examine if mutational status of KIT and PDGFA in patients with imatinib- and sunitinib resistant malignant gastrointestinal stromal tumor correlate with response to BAY 43-9006.
OUTLINE: This is a multicenter study. Patients are stratified according to response to prior treatment with imatinib mesylate and sunitinib malate (imatinib mesylate- and sunitinib malate-responsive disease vs primary imatinib mesylate- and sunitinib malate-refractory disease).
Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637-1470|
|Principal Investigator:||Hedy Kindler||University of Chicago Comprehensive Cancer Center|