Status:
COMPLETED
Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP)
Lead Sponsor:
Cancer Prevention Pharmaceuticals, Inc.
Conditions:
Familial Adenomatous Polyposis
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief Summary
The purpose of this randomized, double-blind, Phase III trial is to determine if the combination of eflornithine plus sulindac is superior to sulindac or eflornithine as single agents in delaying time...
Eligibility Criteria
Inclusion
- Diagnosis of phenotypic classical FAP with disease involvement of the duodenum and/or colon/rectum/pouch.
- Genotype: Adenomatous polyposis coli (APC) mutation (with or without family history) required
- 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:
- 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. \[Note: For staging purposes only.\]
- 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:
- Current Spigelman Stage 3 or 4.
- 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):
- No significant hematologic abnormalities
- White blood cell count (WBC) at least 3,000/mm3
- Platelet count at least 100,000/mm3
- Hemoglobin at least 10.0 g/dL
- No history of clinical coagulopathy
- Hepatic Status (within 30 days prior to randomization):
- Bilirubin no greater than 1.5 times ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than 1.5 times ULN
- 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.
Exclusion
- Prior pelvic irradiation.
- Patients receiving oral corticosteroids within 30 days of enrollment.
- Treatment with other investigational agents in the prior 4 weeks.
- Use of other non-steroidal anti-inflammatory drugs (such as ibuprofen) exceeding 4 days per month, in the prior 6 weeks.
- Regular use of aspirin in excess of 700 mg per week.
- Treatment with other FAP directed drug therapy (including sulindac or celecoxib, fish oil) within 12 weeks of study enrollment.
- Hypersensitivity to cyclooxygenase-2 inhibitors, sulfonamides, NSAIDs, or salicylates; NSAID associated symptoms of gastritis.
- Patients must not have cardiovascular disease risk factors as defined below:
- Uncontrolled high blood pressure (systolic blood pressure \> 150 mm Hg
- Unstable angina
- History of documented myocardial infarction or cerebrovascular accident
- New York Heart Association Class III or IV heart failure
- Known uncontrolled hyperlipidemia defined as LDL-C \>= 190 mg/dL or triglycerides \>= 500 mg/dL
- Patients with significant hearing loss are not eligible for study participation defined as hearing loss that affects everyday life and/or for which a hearing aid is required.
- Colon/rectum/pouch with high grade dysplasia or cancer on biopsy or a large polyp (\>1 cm) not amenable to complete removal.
- Duodenal cancer on biopsy.
- Intra-abdominal desmoid disease, stage III or IV
- Inability to provide informed consent.
Key Trial Info
Start Date :
October 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 1 2019
Estimated Enrollment :
171 Patients enrolled
Trial Details
Trial ID
NCT01483144
Start Date
October 1 2013
End Date
March 1 2019
Last Update
June 8 2021
Active Locations (17)
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1
University of California San Diego
La Jolla, California, United States, 92093
2
Emory University
Atlanta, Georgia, United States, 30322
3
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
4
University of Michigan
Ann Arbor, Michigan, United States, 48109