Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP)

Inclusion Criteria

• •Diagnosis of phenotypic classical FAP with disease involvement of the duodenum and/or colon/rectum/pouch.
• •1. Genotype: Adenomatous polyposis coli (APC) mutation (with or without family history) required
• •2. Classical FAP Phenotype: 100's to 1,000's of colorectal adenomatous polyps, usually appearing in teenage years
• •Upper gastrointestinal (UGI) endoscopy/ lower gastrointestinal (LGI) endoscopy (proctoscopy/colonoscopy) performed within 30 days of randomization.
• •Patients with an intact colon/rectum, except for clinical polyposis, and prophylactic surgery is being considered as a stratification site.
• •Rectal/pouch polyposis as a stratification site as follows:
• •1. At least three years since colectomy with ileorectal anastamosis (IRA)/proctocolectomy with pouch, and demonstrating polyposis as defined by Stage 1, 2, 3, of the proposed InSiGHT 2011 Staging System (Appendix B) and summarized as follows:
• •Stage 1: 10-25 polyps, all \< 5 mm Stage 2: 10-25 polyps, at least one \> 1 cm Stage 3: \>25 polyps amenable to complete removal, or any incompletely removed sessile polyp, or any evidence of high grade dysplasia, even if completely removed. \[Note: For staging purposes only.\]
• •2. For all subjects, any rectal/pouch polyps \> 5 mm must be excised at "baseline".
• •Duodenal polyposis as a stratification site; one or more of the following:
• •1. Current Spigelman Stage 3 or 4.
• •2. Prior surgical endoscopic intervention within the past six months for Spigelman Stage 3 or 4 that may have been down staged to Spigelman Stage 1 or 2.
• •Hematopoietic Status (within 30 days prior to randomization):
• •1. No significant hematologic abnormalities
• •2. White blood cell count (WBC) at least 3,000/mm3
• •3. Platelet count at least 100,000/mm3
• •4. Hemoglobin at least 10.0 g/dL
• •5. No history of clinical coagulopathy
• •Hepatic Status (within 30 days prior to randomization):
• •1. Bilirubin no greater than 1.5 times ULN
• •2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than 1.5 times ULN
• •3. Alkaline phosphatase no greater than 1.5 times ULN
• •Renal Status (within 30 days prior to randomization):
• •a) Creatinine no greater than 1.5 times ULN
• •Hearing:
• •a) No clinically significant hearing loss, defined in Section 6.2, number 9.
• •If female, neither pregnant nor lactating.
• •Negative pregnancy test if female of child-bearing potential. Fertile patients must use effective contraception\*.
• •Absence of gross blood in stool; red blood on toilet paper only acceptable.
• •No discrete gastric or duodenal ulcer greater than 5 mm within the past year except Helicobacter pylori-related peptic ulcer disease treated with antibiotics.
• •No invasive malignancy within the past 5 years except resected non-melanomatous skin cancer, papillary thyroid cancer, or precancerous cervical dysplasia.
• •No other significant medical or psychiatric problems that would preclude study participation or interfere with capacity to give informed consent.
• •Use of 81-100 mg daily aspirin or up to 700 mg aspirin not more than once a week are eligible.
• •No concurrent warfarin, fluconazole, lithium, Pradaxa® or other direct thrombin inhibitors, Plavix®, cyclosporine, other NSAIDs (such as ibuprofen, aspirin, diflunisal), diuretics (furosemide and thiazides), dimethylsulfoxide (DMSO), methotrexate, probenecid, propoxyphene hydrochloride, Tylenol® (acetaminophen) preparations containing aspirin or cytotoxic chemotherapy drugs.
• •Willingness to forego concurrent use of supplements containing omega-3 fatty acids, corticosteroids, non-steroidal anti-inflammatory drugs or other FAP directed drug therapy.
• •Able to provide informed consent and follow protocol requirements.