Atorvastatin Calcium, Oligofructose-Enriched Inulin, or Sulindac in Preventing Cancer in Patients at Increased Risk of Developing Colorectal Neoplasia

Phase 2

Completed

Conditions: Precancerous Condition
Rectal Cancer
Colon Cancer

Interventions: Drug: atorvastatin calcium
Drug: sulindac
Drug: oligofructose-enriched inulin
Drug: placebo
Other: laboratory biomarker analysis

Registration Number: NCT00335504

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This randomized phase II trial is studying atorvastatin calcium to see how well it works compared to oligofructose-enriched inulin, sulindac, or a placebo in preventing cancer in patients at increased risk of developing colorectal neoplasia. Chemoprevention is the use of certain drugs or substances to keep cancer from forming, growing, or coming back. The use of atorvastatin calcium, oligofructose-enriched inulin, or sulindac may stop cancer from forming in patients at increased risk of colorectal neoplasia. It is not yet known whether atorvastatin calcium, oligofructose-enriched inulin, or sulindac are more effective than a placebo in preventing cancer in patients at increased risk of developing colorectal neoplasia.

Detailed Description: PRIMARY OBJECTIVE:

I. Percent change in number of rectal aberrant cryptic foci (ACF) as measured by magnification chromoendoscopy

SECONDARY OBJECTIVES:

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 85

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (atorvastatin calcium)	atorvastatin calcium	Patients receive oral atorvastatin once daily.
Arm I (atorvastatin calcium)	laboratory biomarker analysis	Patients receive oral atorvastatin once daily.
Arm II (sulindac)	sulindac	Patients receive oral sulindac twice daily.
Arm II (sulindac)	laboratory biomarker analysis	Patients receive oral sulindac twice daily.
Arm III (oligofructose-enriched inulin)	oligofructose-enriched inulin	Patients receive oral oligofructose-enriched inulin (Raftilose Synergy 1) twice daily.
Arm III (oligofructose-enriched inulin)	laboratory biomarker analysis	Patients receive oral oligofructose-enriched inulin (Raftilose Synergy 1) twice daily.
Arm IV (placebo)	placebo	Patients receive an oral placebo twice daily.
Arm IV (placebo)	laboratory biomarker analysis	Patients receive an oral placebo twice daily.

Primary Outcome Measures

Name	Time	Method
Percent Change in Number of Rectal Aberrant Cryptic Foci (ACF) as Measured by Magnification Chromoendoscopy	6 months	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.

Secondary Outcome Measures

Name	Time	Method
Effects on Proliferation (Ki67 Expression).	Up to 6 months	Tissue is examined by immunohistochemistry for Ki67. Measured by biopsy samples obtained from normal-appearing rectal mucosa at baseline and after completion of study treatment. Wilcoxon will be used to assess significant differences between the intervention arms.
Effects on Apoptosis (Caspase-3 Expression).	Up to 6 months	Tissue is examined by immunohistochemistry for cleaved caspase-3. Measured by biopsy samples obtained from normal-appearing rectal mucosa at baseline and after completion of study treatment. Wilcoxon will be used to assess significant differences between the intervention arms.
Adverse Events.	Up to 30 days after completion of study treatment	Defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with participation in a study, whether or not related to that participation. Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 3.0. Number of adverse events per grade level.