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
40 Years
80 Years
Both
Colorectal Cancer
Trial Information
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
OBJECTIVES:
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- At least 1 prior resected colorectal adenoma within the past 5 years
- At least 3 mm in size
- No personal or family history of familial adenomatous polyposis
PATIENT CHARACTERISTICS:
Age:
- 40 to 80
Performance status:
- SWOG 0-1
Life expectancy:
- Not specified
Hematopoietic:
- Hematocrit at least 35%
- WBC at least 4,000/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin no greater than 2.0 mg/dL
- AST and ALT no greater than 2 times normal
Renal:
- Creatinine no greater than 1.5 mg/dL
- No greater than 1+ protein, 0-3 casts, and 0-5 WBCs and RBCs in urine
Gastrointestinal:
- No requirement for special diet or additives
- No diet that would preclude taking study medications
- No gastric or duodenal ulcer within the past year
- No inflammatory bowel disease
Other:
- No more than 20 dB hearing loss for age at any frequency
- No prior or concurrent invasive cancer within the past 5 years except nonmelanomatous
skin cancer, melanoma in situ, stage I cervical cancer, stage I colon cancer, or
stage 0 chronic lymphocytic leukemia
- No severe metabolic disorder or other acute or chronic diseases
- No history of or predisposition to abnormal wound healing or repair
- No allergies to nonsteroidal anti-inflammatories or eflornithine
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- No concurrent chemotherapy
Endocrine therapy:
- No concurrent corticosteroids
Radiotherapy:
- No concurrent radiotherapy
Surgery:
- See Disease Characteristics
Other:
- No other concurrent nonsteroidal anti-inflammatories or anticoagulants administered
on a regular or predictable intermittent basis
- No concurrent aspirin greater than 81 mg per day or 325 mg twice a week for
cardiovascular disease prophylaxis
- No concurrent calcium supplements greater than 500 mg/day
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Outcome Measure:
To measure the efficacy of DFMO plus Sulindac versus placebo in modulating biomarkers of colorectal neoplasia.
Outcome Time Frame:
36 months post-randomization
Safety Issue:
No
Principal Investigator
Frank L. Meyskens, MD, FACP
Investigator Role:
Study Chair
Investigator Affiliation:
Chao Family Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000067922
NCT ID:
NCT00005882
Start Date:
June 2000
Completion Date:
December 2011
Related Keywords:
- Colorectal Cancer
- colon cancer
- rectal cancer
- Colorectal Neoplasms
Name | Location |
|---|---|
| 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 |
