Randomized, Phase II Trial of Atorvastatin, RAFTILOSE Synergy 1, and Sulindac Among Patients at Increased Risk for Sporadic Colorectal Neoplasia
I. Percent change in number of rectal aberrant cryptic foci (ACF) as measured by
I. Screening for possible phase III testing II. Effects on proliferation (Ki67 expression)
and apoptosis (caspase-3 expression) as measured by biopsy samples obtained from
normal-appearing rectal mucosa at baseline and after completion of study treatment III.
Correlation of endoscopic features with histologic characteristics of rectal ACF IV.
Observation of the natural history of rectal ACF in patients receiving placebo V. Adverse
events VI. Utilization of a biospecimen repository archive
OUTLINE: This is a multicenter, prospective, randomized, partially blinded,
placebo-controlled study. Patients are stratified according to history of prior surgical
resection of the colon (yes vs no) and number of rectal aberrant cryptic foci (ACF) (5-9 vs
>= 10). Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive oral atorvastatin calcium once daily.
ARM II: Patients receive oral sulindac twice daily.
ARM III (blinded arm): Patients receive oral oligofructose-enriched inulin (Raftilose
Synergy 1) twice daily.
ARM IV (blinded arm): Patients receive an oral placebo twice daily.
In all arms, treatment continues for 6 months in the absence of unacceptable toxicity.
Tissue samples are collected at baseline and at the completion of study treatment. Tissue is
examined by immunohistochemistry for proliferation (Ki67) and apoptosis (cleaved caspase-3).
After completion of study treatment, patients are followed at approximately 30 days.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Percent Change in Number of Rectal Aberrant Cryptic Foci (ACF) as Measured by Magnification Chromoendoscopy
At the Pre-Intervention Evaluation, rectal ACF will be classified with respect to ACF number, crypt number, crypt size, tissue plane, staining intensity, and (optional) lumen shape for each subject. At the Post- Intervention Evaluation, these same parameters will be recorded and incident vs prevalent rectal ACF status will also be recorded. Compare each non-placebo arms versus the placebo arm to screen the three active study agents for possible phase III testing.
United States: Food and Drug Administration
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