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

NCT00118365 | Completed Phase 3 Results

• 3 other identifiers: NCI-2009-00880UCI 97-05R01CA088078
• Study Type: interventional
• Target: 375
• Locations: 1 country
• Sites: 1

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

Conditions

Precancerous Condition

Outcome Measures

Primary Outcomes (1)

• Detection of Any Adenoma at the End of the Study

  Detection of any adenoma at the end of the study. This analysis is based on the participants who had the end-of-study colonscopy procedure done.

  Up to 36 months

Secondary Outcomes (20)

• Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment

  Up to 36 months

• Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment

  Up 36 months

• Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment

  Up 36 months

• Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment

  Up to 36 months

• Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment

  Up to 36 months

Study Arms (2)

Arm II (placebo)

PLACEBO COMPARATOR

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.

Other: placebo; Other: laboratory biomarker analysis

Arm I (eflornithine and sulindac)

EXPERIMENTAL

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.

Drug: eflornithine; Drug: sulindac; Other: laboratory biomarker analysis

Interventions

placebo OTHER

Given orally

Also known as: PLCB

Arm II (placebo)

eflornithine DRUG

Given orally

Also known as: 2-difluoromethylornithine, DFMO, difluromethylornithine

Arm I (eflornithine and sulindac)

sulindac DRUG

Given orally

Also known as: Aflodac, Algocetil, Clinoril, SULIN

Arm I (eflornithine and sulindac)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (eflornithine and sulindac); Arm II (placebo)

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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)

University of California Medical Center At Irvine-Orange Campus

Orange, California, 92868, United States

Location

Related Publications (1)

• 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.

  PMID: 20538001 DERIVED

MeSH Terms

Conditions

Precancerous Conditions

Interventions

Eflornithine; Sulindac

Condition Hierarchy (Ancestors)

Neoplasms

Intervention Hierarchy (Ancestors)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Frank Meyskens, Jr.
• Organization: University of California, Irvine

flmeyske@uci.edu

714-456-6310

Study Officials

• Frank Meyskens

  University of California Medical Center At Irvine-Orange Campus

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2005
• First Posted: July 11, 2005
• Study Start: July 1, 1998
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: January 22, 2015
• Results First Posted: January 22, 2015

Record last verified: 2014-02

Locations

US (1)