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

NCT00335504 | Completed Phase 2 Results

• 5 other identifiers: NCI-2009-00837CDR0000467755MAY03-1-03N01CN35000P30CA015083
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

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.

Conditions

Colon Cancer; Precancerous Condition; Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (3)

• Effects on Proliferation (Ki67 Expression).

  Up to 6 months

• Effects on Apoptosis (Caspase-3 Expression).

  Up to 6 months

• Adverse Events.

  Up to 30 days after completion of study treatment

Study Arms (4)

Arm I (atorvastatin calcium)

EXPERIMENTAL

Patients receive oral atorvastatin once daily.

Drug: atorvastatin calcium; Other: laboratory biomarker analysis

Arm II (sulindac)

EXPERIMENTAL

Patients receive oral sulindac twice daily.

Drug: sulindac; Other: laboratory biomarker analysis

Arm III (oligofructose-enriched inulin)

EXPERIMENTAL

Patients receive oral oligofructose-enriched inulin (Raftilose Synergy 1) twice daily.

Drug: oligofructose-enriched inulin; Other: laboratory biomarker analysis

Arm IV (placebo)

PLACEBO COMPARATOR

Patients receive an oral placebo twice daily.

Drug: placebo; Other: laboratory biomarker analysis

Interventions

oligofructose-enriched inulin DRUG

Given orally

Also known as: Beneo Synergy 1, Synergy 1

Arm III (oligofructose-enriched inulin)

sulindac DRUG

Given orally

Also known as: Aflodac, Algocetil, Clinoril, SULIN

Arm II (sulindac)

placebo DRUG

Given orally

Also known as: PLCB

Arm IV (placebo)

atorvastatin calcium DRUG

Given orally

Also known as: CI-981, Lipitor

Arm I (atorvastatin calcium)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (atorvastatin calcium); Arm II (sulindac); Arm III (oligofructose-enriched inulin); Arm IV (placebo)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Criteria: * ECOG performance status 0-2 * Platelet count \>= 100,000/mm\^3 * Fertile patients must agree to use effective contraception * No history of inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis) * No invasive malignancy within the past 5 years except nonmelanoma skin cancer or colorectal cancer * No history of endoscopically-confirmed peptic ulcer disease * No history of allergic reactions attributed to compounds of similar chemical or biological composition to the study agents * No history of chronic liver disease or unexplained persistent elevations of serum transaminases * No history of allergic-type reactions, including asthma or urticaria, to aspirin or NSAIDs * No uncontrolled intercurrent illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness or social situations that would preclude study compliance * At least 6 weeks since prior oral corticosteroids * Creatinine =\< 1.5 times ULN * Creatine phosphokinase =\< 1.5 times ULN * Not pregnant or nursing * At least 6 weeks since prior statins * At increased risk for developing sporadic colorectal neoplasia, as defined by 1 of the following: * History of colon cancer (excluding stage IV or Dukes' D tumors) * Must have completed prior adjuvant therapy for colon cancer \>= 12 months ago * History of colorectal adenomas, meeting any of the following criteria: * \>= 1 cm in diameter * \>= 3 in total number * Any component of villous morphology * High-grade dysplasia * At least 5 rectal aberrant cryptic foci (ACF), by magnification chromoendoscopy, meeting both of the following criteria: * At least 5 aggregated crypts in a single grouping (maximum spacing between crypts must be =\< 2 times the average crypt diameter) * Crypt diameter \>= 1.5 times the diameter of surrounding normal crypts * No history of rectal cancer, familial adenomatous polyposis, or hereditary nonpolyposis colorectal cancer * Negative pregnancy test * At least 6 months since prior and no concurrent regular use\* of nonsteroidal anti-inflammatory drugs\*\* (NSAIDs) or statins * Concurrent aspirin at cardioprotective doses (=\< 162.5 mg/day or 325 mg every other day) allowed * No prior rectal surgery involving mucosal resection * No prior pelvic radiation therapy * No concurrent regular use\* of cyclooxygenase-2 inhibitors * No concurrent anticoagulant drugs (i.e., warfarin, heparin, clopidogrel bisulfate, or extended-release dipyridamole) * No concurrent use of any of the following: * Fibrates (e.g., gemfibrozil or fenofibrate) * Cyclosporine * Erythromycin or macrolide antibiotics * Protease inhibitors * Azole antifungals * Diltiazem * Verapamil * Compounds containing niacin or nicotinic acid * Defined as 7 consecutive days for \> 3 weeks OR \> 21 days total during study participation * Patients may be eligible for study treatment after discontinuing NSAIDs for 12 weeks, at the discretion of their health care provider * No other concurrent investigational agents * No planned (or likely to require) clinically indicated colonoscopy or flexible sigmoidoscopy during study treatment * Bilirubin =\< 1.5 times ULN * Hemoglobin \>= lower limit of normal * AST =\< 1.5 times upper limit of normal (ULN) * Alkaline phosphatase =\< 1.5 times ULN

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Precancerous Conditions; Rectal Neoplasms

Interventions

Sulindac; Atorvastatin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Limitations and Caveats

Variation in endpoint measurement across sites, relatively small sample size, and rectal biomarker assessments only may have contributed to challenges in full data interpretation.

Results Point of Contact

• Title: Dr. Paul Limburg
• Organization: Mayo Clinic

limburg.paul@mayo.edu

507-266-9093

Study Officials

• Paul Limburg

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2006
• First Posted: June 12, 2006
• Study Start: March 1, 2006
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: February 15, 2017
• Results First Posted: February 8, 2013

Record last verified: 2016-12

Locations

US (1)