A Randomized Phase III Trial Of Gemcitabine Plus Bevacizumab (NSC#704865 IND#7621) Versus Gemcitabine Plus Placebo In Patients With Advanced Pancreatic Cancer
I. To determine if combination chemotherapy with gemcitabine and bevacizumab achieves
superior survival compared to gemcitabine and placebo in patients with previously untreated
advanced pancreatic cancer.
I. To compare the objective response rates, duration of response, progression free survival,
and toxicity of these two regimens in patients with advanced pancreatic cancer.
II. To measure baseline levels of VEGF and correlate with treatment outcome. III. To measure
baseline and on treatment levels of additional growth factors that may be co- or counter-
regulated with VEGF and correlate with response to treatment.
IV. To measure baseline and on treatment levels of coagulation and endothelial cell
activation markers that may predict for thrombotic or bleeding risks related to treatment.
V. To generate protein expression profiles using a MALDI-TOF based platform from serum
samples. To analyze and compare protein expression profiles to elucidate ion peaks that
differentiate patients who respond to therapy from patients who do not respond. To identify
proteins responsible for the differentially expressed ion peaks. To develop quantitative
assays for each of these proteins.
VI. To assess any differences in overall survival within the treatment arm (gemcitabine +
bevacizumab), between the two VEGF genotypic groups: Group 1 denoted by individuals with CT
or TT genotypes and Group 2 consisting of individuals with CC genotypes.
VII. To conduct an exploratory analysis of gene-toxicity, gene-response, and gene-survival
relationships for the various polymorphisms described in the genes implicated in gemcitabine
pharmacology (CDA, DCK, DCTD, SLC29A1, SLC28A1, SLC29A2). An exploratory quantitative
interaction between the genotypes (group 1 or 2) and the treatment arms (gemcitabine +
bevacizumab or gemcitabine + placebo) in predicting overall survival will also be evaluated.
VIII. To identify specific SNPs and genetic variation that are associated with differences
among patients in the risk of toxicity.
IX. To compare the effects of gemcitabine + bevacizumab versus gemcitabine + placebo on
resource utilization, cost, and utilities, and if applicable, to make estimates of marginal
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to ECOG performance status (0-1 vs 2), disease extent (metastatic
vs locally advanced), and prior radiotherapy (yes vs no). Patients are randomized to 1 of 2
Arm I: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and bevacizumab
IV over 30-90 minutes on days 1 and 15.
Arm II: Patients receive gemcitabine IV as in arm I and placebo IV over 30-90 minutes on
days 1 and 15.
In both arms, courses repeat every 28 days in the absence of disease progression or
Patients are followed every 3 months for 1 year and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 590 patients (295 per treatment arm) will be accrued for this
study within 26.8 months.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Overall survival (OS)
Based on the stratified logrank test.
From trial entry until death, assessed up to 7 years
Cancer and Leukemia Group B
United States: Food and Drug Administration
|Cancer and Leukemia Group B||Chicago, Illinois 60606|