A Trial of Low Dose Sulindac Combined With Eflornithine in Patients With Familial Adenomatous Polyposis (FAP)

NCT01245816 | Withdrawn Phase 3 DMC

• 1 other identifier: CPP FAP-301
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this phase III study is to evaluate the safety and efficacy of the combination of eflornithine and sulindac compared to single agent sulindac or eflornithine in reducing the number of polyps in patients with familial adenomatous polyposis (FAP).

Conditions

Familial Adenomatous Polyposis

Keywords

colon polyps

Outcome Measures

Primary Outcomes (1)

• Efficacy of Eflornithine plus Sulindac compared to Eflornithine alone and Sulindac alone determined by change in the number of polyps 2 mm or greater in a defined focal area of the rectum or pouch at baseline and after completion of the study treatment.

  6 months from the start of treatment.

Secondary Outcomes (3)

• Change in number of polyps 2 mm or greater in the distal 10 cm of rectum or pouch.

  6 months from the start of treatment.

• Qualitative change in overall colon/rectum/pouch polyp burden (number and size).

  6 months from the start of treatment.

• Presence of high grade dysplasia or villous adenoma in any polyp resected.

  6 months from the start of treatment.

Study Arms (3)

Eflornithine plus Sulindac

EXPERIMENTAL

Eflornithine 500 mg and Sulindac 150 mg

Drug: Eflornithine plus Sulindac

Elfornithine plus Placebo

ACTIVE COMPARATOR

Eflornithine 500 mg and Placebo

Drug: Eflornithine plus Placebo

Sulindac plus Placebo

ACTIVE COMPARATOR

Sulindac 150 mg and Placebo

Drug: Sulindac plus Placebo

Interventions

Eflornithine plus Sulindac DRUG

Eflornithine, 250 mg tablet, two tablets (500 mg) orally once a day; Sulindac, 150 mg tablet, one tablet orally once a day

Also known as: DFMO

Eflornithine plus Sulindac

Eflornithine plus Placebo DRUG

Eflornithine, 250 mg tablet, two tablets (500 mg) orally once a day; Placebo, one tablet orally once a day

Also known as: DFMO

Elfornithine plus Placebo

Sulindac plus Placebo DRUG

Sulindac, 150 mg tablet, one tablet orally once a day; Placebo, two tablets orally once a day

Sulindac plus Placebo

Eligibility Criteria

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

You may qualify if:

• Diagnosis of phenotypic Familial Adenomatous Polyposis (FAP) of the colorectum based on meeting the criteria in one of two groups: Group 1-Greater than 100 adenomatous colorectal polyps prior to age 40. Group 2-Greater than 10 adenomatous polyps and age \<40 or greater than 25 polyps and age \>40; combined with a dominant family history or genotype: More than 100 polyps in a first-degree relative; More than 25 polyps in 2 relatives in 2 generations, including a first-degree family member; Genetic diagnosis in a relative; Genetic diagnosis by in vitro synthesized truncated protein or similar assay.
• No colorectal surgery or prior colon surgery for polyposis at least 1 year prior (total abdominal colectomy with ileal-rectal anastomosis, or total proctocolectomy with ilea pouch-anal reconstruction.
• Baseline endoscopy
• If no prior colorectal surgery, at least 3 polyps in a cluster each ≥ 2 mm in diameter; or
• If rectum is in situ and to be assessed, baseline rectal segment endoscopy documenting 3 or more rectal polyps each at least 2 mm in diameter in a defined cluster and/or at least 6 polyps, ≥ 2 mm in diameter, in the distal 10 cm of rectum
• If ileal pouch neo-rectum is in place, 3 or more pouch polyps in a cluster ≥ 2 mm in diameter, or at least 6 polyps, ≥ 2 mm in diameter, in the distal 10 cm of pouch.
• Clinical/pathological grading of duodenal polyps will utilize the Spigelman Classification.
• Hematopoietic: no significant hematologic dysfunction; WBC ≥3,000/mm3; platelet count ≥100,000/mm3; hemoglobin ≥10g/dL; no known or prior clinical coagulopathy.
• Hepatic: bilirubin ≤ 1.5 times ULN; AST and ALT ≤ 1.5 times ULN; Alkaline phosphatase ≤ 1.5 times ULN.
• Renal: No significant renal dysfunction; creatinine ≤ 1.5 times ULN.
• Hearing: no clinically significant hearing loss that affects everyday life.
• Not pregnant or nursing.
• Negative serum pregnancy test if female of child-bearing potential.
• Absence of gross blood in stool.
• Fertile patients must use effective contraception.

You may not qualify if:

• High Risk for cardiovascular disease including clinical diabetes mellitus (Type I or II) requiring glycemic medications; Prior personal history of cardiovascular disease or, two or more of the following - hypertension or use of anti-hypertensive medications, hyperlipidemia or use of lipid-lowering medications or current smoker.
• Hearing loss that affects everyday life and or for which a hearing aid is required.

Sponsors & Collaborators

• Cancer Prevention Pharmaceuticals, Inc.: lead

MeSH Terms

Conditions

Adenomatous Polyposis Coli; Colonic Polyps

Interventions

Eflornithine; Sulindac

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Intestinal Polyps; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

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

Study Officials

• Alfred M. Cohen, M.D.

  Cancer Prevention Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 19, 2010
• First Posted: November 23, 2010
• Study Start: March 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: June 1, 2013
• Last Updated: April 24, 2015

Record last verified: 2015-04