Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Cancer Prevention Pharmaceuticals, Inc. Identifier:
First received: November 21, 2011
Last updated: April 11, 2016
Last verified: April 2016
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 to the first occurrence of any FAP-related event. This includes: 1) FAP related disease progression indicating the need for excisional intervention involving the colon, rectum, pouch, duodenum and/or 2) clinically important events which includes progression to more advanced duodenal polyposis, cancer or death.

Condition Intervention Phase
Familial Adenomatous Polyposis
Drug: Eflornithine plus Sulindac
Drug: Eflornithine and Placebo
Drug: Sulindac and Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Phase III Trial of the Safety and Efficacy of Eflornithine Combined With Sulindac Compared to Eflornithine, Sulindac as Single Agents in Patients With Familial Adenomatous Polyposis

Resource links provided by NLM:

Further study details as provided by Cancer Prevention Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Delaying time to the 1st occurrence of any FAP-related event. [ Time Frame: 24 months from the start of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • presence or absence of an ODC polymorphism [ Time Frame: 24 months from the start of treatment ] [ Designated as safety issue: No ]
    evaluate the potentially effect modifying properties of an ornithine decarboyxlase (ODC) polymorphism on primary outcome

  • excretion of 4 urinary polyamines [ Time Frame: 24 months from the start of treatment ] [ Designated as safety issue: No ]
    evaluate the potentially effect modifying properties of 4 urinary polyamines

Other Outcome Measures:
  • Analysis of adverse events and clinical laboratory abnormalities indicating possible adverse events [ Time Frame: 24 months from the start of treatment ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (AUC, Cmax, Cmin, tmax, Css, CL) of study medication [ Time Frame: pre-dose and 1, 2, 4, and 8 hours post-dose (5 time points at month 3) ] [ Designated as safety issue: No ]
  • Evaluate tissue and dietary polyamine levels [ Time Frame: 24 months from the start of treatment ] [ Designated as safety issue: No ]
  • Patient reported quality of life will be evaluated using health related quality of life questionnaires and patient utilities [ Time Frame: 24 months from the start of treatment ] [ Designated as safety issue: No ]
  • Evaluation of the time to the first FAP-related beneficent event [ Time Frame: 24 months from the start of treatment ] [ Designated as safety issue: No ]

Enrollment: 171
Study Start Date: October 2013
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eflornithine plus Sulindac
Eflornithine 750 mg and Sulindac 150 mg
Drug: Eflornithine plus Sulindac
Eflornithine [250 mg tablet, three tablets (750 mg) orally once a day] and Sulindac [150 mg tablet, one tablet orally once a day] for 24 months
Active Comparator: Eflornithine plus Placebo
Eflornithine 750 mg and Placebo
Drug: Eflornithine and Placebo
Eflornithine [250 mg, three tablets (750 mg) orally once a day] and Placebo [one tablet orally once a day] for 24 months
Active Comparator: Sulindac plus Placebo
Sulindac 150 mg and Placebo
Drug: Sulindac and Placebo
Sulindac [150 mg tablet, one tablet orally once a day] and Placebo [three tablets orally once a day] for 24 months


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of phenotypic classical FAP with disease involvement of the duodenum and/or colon/rectum/pouch.

    1. Genotype: 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
  • UGI endoscopy/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 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. (Refer to Appendix A for Modified Spigelman Score and Classification table).
    2. Prior surgical endoscopic intervention within the past six months for Spigelman Stage 3 or 4 that may have been down staged to Spigelman 1 or 2.
  • Hematopoietic Status (within 30 days prior to randomization):

    1. No significant hematologic abnormalities
    2. 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. AST and 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), 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 Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01483144

  Show 21 Study Locations
Sponsors and Collaborators
Cancer Prevention Pharmaceuticals, Inc.
Principal Investigator: Carol Burke, M.D. The Cleveland Clinic
Principal Investigator: James Church, M.D. The Cleveland Clinic
Principal Investigator: Gabriella Möslein, M.D. Helios Hospital
  More Information

Additional Information:
Responsible Party: Cancer Prevention Pharmaceuticals, Inc. Identifier: NCT01483144     History of Changes
Other Study ID Numbers: CPP-FAP-310 
Study First Received: November 21, 2011
Last Updated: April 11, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
European Union: European Medicines Agency

Keywords provided by Cancer Prevention Pharmaceuticals, Inc.:
Familial Adenomatous Polyposis

Additional relevant MeSH terms:
Colorectal Neoplasms
Nasopharyngeal Neoplasms
Adenomatous Polyposis Coli
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Adenomatous Polyps
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplastic Syndromes, Hereditary
Intestinal Polyposis
Genetic Diseases, Inborn
Anti-Inflammatory Agents, Non-Steroidal processed this record on October 21, 2016