Eflornithine and Sulindac in Preventing Colorectal Cancer in Patients With Colon Polyps

NCT ID: NCT00118365

Last Updated: 2015-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 375 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-07-31
• Study Completion Date: 2008-08-31

Brief Summary

This randomized phase III trial is studying eflornithine and sulindac to see how well they work compared to a placebo in preventing colorectal cancer in patients with colon polyps. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of eflornithine and sulindac may prevent colorectal cancer. It is not yet known whether eflornithine and sulindac are more effective than a placebo in preventing colorectal cancer

Detailed Description

PRIMARY OBJECTIVES:

I. Compare the rate of new adenomatous polyp formation in patients with a history of adenomatous polyps of the colon treated with eflornithine and sulindac vs placebo.

II. Correlate the effects of eflornithine and sulindac on polyamine and prostaglandin content in the flat mucosa with the rate of new adenoma formation in these patients.

III. Compare the rate of side effects in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center and aspirin use (yes vs no).

Patients receive oral double placebo once daily for 4 weeks. Patients who are more than 70% compliant by pill measurement or self reporting are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral double placebo once daily.

Arm II: Patients receive oral eflornithine (DFMO) and oral sulindac once daily.

In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

Conditions

Precancerous Condition

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Arm II (placebo)

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Given orally

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Arm I (eflornithine and sulindac)

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

Group Type: EXPERIMENTAL

eflornithine

Intervention Type: DRUG

Given orally

sulindac

Intervention Type: DRUG

Given orally

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

placebo

Given orally

Intervention Type: OTHER

eflornithine

Given orally

Intervention Type: DRUG

sulindac

Given orally

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

PLCB; 2-difluoromethylornithine; DFMO; difluromethylornithine; Aflodac; Algocetil; Clinoril; SULIN

Eligibility Criteria

Inclusion Criteria

Criteria:

• History of >= 1 surgically resected adenomatous polyp of the colon measuring >= 3 mm within the past 5 years
• Screening colonoscopy performed within the past 6 months
• All polyps must have been removed during colonoscopy, pathologically examined, and archived
• No prior surgical resection removing > 40 cm of the colon
• No personal or family history of familial polyposis or hereditary non-polyposis colon cancer
• SWOG 0-1
• Bilirubin =< 2.0 mg/dL
• AST and ALT =< 2 times normal
• Creatinine =< 1.5 mg/dL
• Urine protein =<, urine casts 0-3, urine WBC and RBC count 0-5 cells by urinalysis
• No history of inflammatory bowel disease
• No gastric or duodenal ulcers within the past 12 months
• Gastric or duodenal ulcers that were adequately treated > 24 months ago are allowed
• No symptomatic gastric or duodenal ulcers
• Not pregnant or nursing
• Negative pregnancy test
• Must have regional geographic stability over the next 36 months
• Pure tone audiometry evaluation normal
• Patients with >= 20 dB of uncorrectable hearing loss (for age) of any 2 contiguous frequencies are not allowed
• No invasive malignancy within the past 5 years except adequately treated nonmelanoma skin cancer, level I (or Breslow < 0.76 mm) cutaneous melanoma, Duke's A colon cancer, stage I cervical cancer, or stage 0 chronic lymphocytic leukemia
• No severe metabolic disorder
• No other significant acute or chronic disease that would preclude study participation
• No history of abnormal wound healing or repair
• No conditions that would confer risk of abnormal wound healing or repair
• No history of allergy to NSAIDs or eflornithine
• No concurrent chemotherapy
• No concurrent corticosteroids on a regular or predictable intermittent basis
• No concurrent radiotherapy
• Concurrent calcium supplements (=< 1,000 mg/day) allowed
• Concurrent lipid-lowering drugs (i.e., high-dose statins) allowed
• No other concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) on a regular or predictable intermittent basis
• Concurrent aspirin for cardiovascular prophylaxis (i.e., 81 mg/day) allowed
• No concurrent anticoagulants on a regular or predictable intermittent basis
• No concurrent treatment for gastric or duodenal ulcers

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frank Meyskens

Role: PRINCIPAL_INVESTIGATOR

University of California Medical Center At Irvine-Orange Campus

Locations

University of California Medical Center At Irvine-Orange Campus

Orange, California, United States

Countries

United States

References

Thompson PA, Wertheim BC, Zell JA, Chen WP, McLaren CE, LaFleur BJ, Meyskens FL, Gerner EW. Levels of rectal mucosal polyamines and prostaglandin E2 predict ability of DFMO and sulindac to prevent colorectal adenoma. Gastroenterology. 2010 Sep;139(3):797-805, 805.e1. doi: 10.1053/j.gastro.2010.06.005. Epub 2010 Jun 9.

Reference Type: DERIVED

PMID: 20538001 (View on PubMed)

Other Identifiers

UCI 97-05

Identifier Type: -

Identifier Source: secondary_id

R01CA088078

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00880

Identifier Type: -

Identifier Source: org_study_id

NCT00005882

Identifier Type: -

Identifier Source: nct_alias