A Double Blind, Placebo Controlled Randomized Phase II Trial Of Gemcitabine And Cisplatin With Or Without The VEGF Inhibitor Bevacizumab (NSC #704865) In Patients With Malignant Mesotheloma
I. Compare the time to progression of patients with malignant mesothelioma treated with
gemcitabine and cisplatin with or without bevacizumab.
II. Compare the objective response rate in patients treated with these regimens.
III. Compare the toxicity of these regimens when administered to these patients.
IV. Compare the median and overall survival of patients treated with these regimens.
V. Assess plasma vascular endothelial growth factor and serum vascular cell adhesion
molecule-1 levels before, during, and after study therapy as predictors of outcome in these
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to histology (epithelial vs other) and ECOG performance status (0
vs 1). Patients are randomized to one of two treatment arms.
ARM I: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and cisplatin IV over
30-60 minutes (beginning after gemcitabine infusion) and bevacizumab IV over 30-90 minutes
(beginning after cisplatin infusion) on day 1. Treatment repeats every 3 weeks for 6 courses
in the absence of disease progression or unacceptable toxicity. Patients who achieve stable
disease (SD), complete response (CR), or partial response (PR) after the sixth course may
receive bevacizumab as a single agent once every 3 weeks in the absence of disease
progression or unacceptable toxicity.
ARM II: Patients receive gemcitabine and cisplatin as in arm I and placebo IV over 30-90
minutes (beginning after cisplatin infusion) on day 1. Treatment repeats as in arm I.
Patients who achieve SD, CR, or PR after the sixth course may receive placebo as a single
agent once every 3 weeks in the absence of disease progression.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Time to disease progression
The two treatment groups will be compared using a stratified logrank test. Kaplan-Meier time-to-event curves will be constructed for each treatment group. Median time-to-progression in each group and corresponding 95% confidence intervals will be derived using the method described in Brookmeyer and Crowley; stratum-specific inference for median event times will be performed as described in Karrison.
Time from randomization until the first evidence of progression, up to 9 years
University of Chicago Comprehensive Cancer Center
United States: Food and Drug Administration
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|