start date: March 2011
estimated completion: May 2013
last updated: April 24, 2015
phase of development: Phase 3
study design:
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
primary outcomes:
- 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. [ Time Frame: 6 months from the start of treatment. ] [ Designated as safety issue: No ]
secondary outcomes:
- Change in number of polyps 2 mm or greater in the distal 10 cm of rectum or pouch. [ Time Frame:6 months from the start of treatment. ] [ Designated as safety issue:No ]
- Qualitative change in overall colon/rectum/pouch polyp burden (number and size). [ Time Frame:6 months from the start of treatment. ] [ Designated as safety issue: No ]
- Presence of high grade dysplasia or villous adenoma in any polyp resected. [ Time Frame:6 months from the start of treatment. ] [ Designated as safety issue: No ]
inclusion criteria:
• Eligible Sexes:
- 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; 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.
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