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

Familial Adenomatous Polyposis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01245816
• Other study ID #: CPP FAP-301
• Status: Withdrawn
• Phase: Phase 3
• First received: November 19, 2010
• Last updated: April 23, 2015
• Start date: March 2011
• Est. completion date: June 2013

Study information

• Verified date: April 2015
• Source: Cancer Prevention Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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

1. If no prior colorectal surgery, at least 3 polyps in a cluster each = 2 mm in diameter; or

2. 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

3. 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.

4. 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.

• Stool occult blood either negative or minimal (1+).

• No prior hypersensitivity to cyclooxygenase-2 inhibitors, sulfonamides, NSAIDs, or salicylates; no NSAID associated symptoms of gastritis.

• No discrete gastric or duodenal ulcer greater than 5 mm within the past year except Helicobacter pylori-related peptic ulcer disease treated successfully with antibiotics (as documented by an endoscopy.

• No invasive malignancy within the past 5 years except stage I or II colon or rectal cancer or resected nonmelanomatous skin cancer.

• No other significant medical or psychiatric problems that would preclude study participation.

• No chronic adrenocorticosteroids.

• No prior pelvic irradiation.

• At least 3 months since prior investigational agents.

• Patients may not be receiving or plan to receive corticosteroids.

• Concomitant NSAID use outside this study may not exceed 4 days per month.

• Use of 81 mg daily aspirin or 650 mg aspirin not more than once a week.

• No concurrent warfarin, fluconazole, or lithium.

• Must be willing and able to sign informed consent.

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenomatous Polyposis Coli
• Familial Adenomatous Polyposis

Intervention

Drug:
• Eflornithine plus Sulindac
Eflornithine, 250 mg tablet, two tablets (500 mg) orally once a day; Sulindac, 150 mg tablet, one tablet orally once a day
• Eflornithine plus Placebo
Eflornithine, 250 mg tablet, two tablets (500 mg) orally once a day; Placebo, one tablet orally once a day
• Sulindac plus Placebo
Sulindac, 150 mg tablet, one tablet orally once a day; Placebo, two tablets orally once a day

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cancer Prevention Pharmaceuticals, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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.	No
Secondary	Qualitative change in overall colon/rectum/pouch polyp burden (number and size).		6 months from the start of treatment.	No
Secondary	Presence of high grade dysplasia or villous adenoma in any polyp resected.		6 months from the start of treatment.	No