A Phase II Clinical Trial of a Randomized, Double-Blind, Placebo Controlled Clinical Trial of DFMO and Sulindac Against Various Endpoints of Colorectal Pathobiology in a Cohort of Individuals at Increased Risk of Colorectal Carcinoma
- Compare the efficacy of eflornithine (DFMO) and sulindac vs placebo in modulating a
panel of surrogate endpoint biomarkers (SEB) of particular relevance in colorectal
neoplasia, including quantitative histopathology, uninduced apoptosis, proliferative
(Ki67) and preneoplastic (CEA, sialyl-TN, p53, and bcl-2) features, and polyamine and
PGE2 levels in patients with at least one previously resected colorectal adenoma.
- Determine the relationship between the modulation of SEB in flat mucosa and the
development of interval incident colorectal adenomas in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to aspirin use (yes vs no) and participating center.
Patients receive oral placebo daily for the first 4 weeks. Patients who are compliant and
take the placebo 5 to 7 days each week are randomized to one of two treatment arms.
- Arm I: Patients receive oral sulindac and oral eflornithine (DFMO) daily.
- Arm II: Patients receive oral placebo daily. Treatment continues for 3 years in the
absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: Approximately 240 patients (120 per treatment arm) will be accrued for
this study within 18 months.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
To measure the efficacy of DFMO plus Sulindac versus placebo in modulating biomarkers of colorectal neoplasia.
36 months post-randomization
Frank L. Meyskens, MD, FACP
Chao Family Comprehensive Cancer Center
United States: Food and Drug Administration
|Arizona Cancer Center||Tucson, Arizona 85724|
|Chao Family Comprehensive Cancer Center||Orange, California 92868|
|University of Colorado Cancer Center||Denver, Colorado 80262|
|Veterans Affairs Medical Center - Loma Linda (Pettis)||Loma Linda, California 92357|