A Randomized, Double Blind Placebo Controlled Phase 2 Study of FOLFOX Plus or Minus GDC-0449 in Patients With Advanced Gastric and Gastroesophageal Junction (GEJ) Carcinoma
I. To determine if the addition of hedgehog antagonist GDC-0449 (GDC-0449) to FOLFOX
chemotherapy improves median progression-free survival (PFS) in the first-line treatment of
patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
II. To determine the level of baseline hedgehog-pathway activation and correlate with
clinical outcome and response to treatment with GDC-0449.
III. To determine a primary gastric cancer gene expression profile that may predict response
IV. To determine if serum shed collagen epitopes correlate with clinical outcome and may be
used to assess efficacy of GDC-0449 treatment.
V. To determine if circulating endothelial progenitor cells (EPCs) correlate with treatment
response and may be used to assess efficacy of GDC-0449 treatment.
VI. To determine if serum expression of VEGF, TGF-β, and IGFBP 3 correlate with clinical
outcome and may be used to assess efficacy of GDC-0449 treatment.
I. To determine if the addition of GDC-0449 to FOLFOX chemotherapy increases overall
II. To determine if the addition of GDC-0449 to FOLFOX chemotherapy increases response rate.
III. To determine if the addition of GDC-0449 to FOLFOX chemotherapy affects toxicity rates.
IV. To assess the hedgehog-pathway expression in those patients who consent to repeat biopsy
at week 4-5 and compare to baseline values and clinical outcome.
OUTLINE: This is a multicenter study. Patients are stratified according to institution and
disease status (advanced vs metastatic). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours,
leucovorin calcium IV over 2 hours, and fluorouracil IV over 46-48 hours on day 1. Patients
also receive oral placebo once daily on days 1-14.
ARM II: Patients receive FOLFOX chemotherapy as in arm I. Patients also receive oral
hedgehog antagonist GDC-0449 on days 1-14. In both arms, treatment repeats every 2 weeks in
the absence of unacceptable toxicity or disease progression.
Tumor tissue and blood samples are collected and analyzed for gene expression and
After completion of study treatment, patients are followed every 3 months.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Median progression-free survival
New York Cancer Consortium
United States: Food and Drug Administration
|Albert Einstein College of Medicine||Bronx, New York 10461|
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|
|Loyola University Medical Center||Maywood, Illinois 60153|
|Ingalls Memorial Hospital||Harvey, Illinois 60426|
|Beth Israel Medical Center||New York, New York 10003|
|Weill Medical College of Cornell University||New York, New York 10021|
|Montefiore Medical Center||Bronx, New York 10467-2490|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Columbus, Ohio 43210-1240|
|Crossroads Cancer Center||Effingham, Illinois 62401|
|Memorial Medical Center||Springfield, Illinois 62781|
|University of Pittsburgh||Pittsburgh, Pennsylvania 15261|
|Vanderbilt University||Nashville, Tennessee 37232-6305|
|Indiana University Medical Center||Indianapolis, Indiana 46202|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|Decatur Memorial Hospital||Decatur, Illinois 62526|
|Virginia Commonwealth University||Richmond, Virginia|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Evanston CCOP-NorthShore University HealthSystem||Evanston, Illinois 60201|
|Illinois Oncology Research Association CCOP||Peoria, Illinois 61615|
|Illinois CancerCare-Peoria||Peoria, Illinois 61615|
|Fort Wayne Medical Oncology and Hematology Inc - State Boulevard||Fort Wayne, Indiana 46845|
|Saint John's Mercy Medical Center||Saint Louis, Missouri 63141|
|New York University Langone Medical Center||New York, New York 10016|
|Saint Luke's Roosevelt Hospital Center - Saint Luke's Division||New York, New York 10025|
|Columbia University Medical Center||New York, New York 10032|
|University of Michigan University Hospital||Ann Arbor, Michigan 48109|
|Cancer Care Center of Decatur||Decatur, Illinois 62526|
|New York Cancer Consortium||New York, New York 10016|