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Trial record 1 of 1 for:    NCT01483144
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Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01483144
Recruitment Status : Completed
First Posted : December 1, 2011
Last Update Posted : March 24, 2021
Information provided by (Responsible Party):
Cancer Prevention Pharmaceuticals, Inc.

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 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 or disease Intervention/treatment Phase
Familial Adenomatous Polyposis Drug: Eflornithine Drug: Eflornithine Placebo Drug: Sulindac 150 MG Drug: Sulindac placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 171 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, 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
Study Start Date : October 2013
Actual Primary Completion Date : November 2018
Actual Study Completion Date : March 2019

Arm Intervention/treatment
Experimental: Eflornithine plus Sulindac
Eflornithine 750 mg and Sulindac 150 mg
Drug: Eflornithine
Eflornithine [250 mg tablet, three tablets (750 mg) orally once a day]
Other Name: CPP-1X

Drug: Sulindac 150 MG
Sulindac [one tablet orally once a day]
Other Name: Clinoril

Active Comparator: Eflornithine plus Sulindac Placebo
Eflornithine 750 mg and Placebo
Drug: Eflornithine
Eflornithine [250 mg tablet, three tablets (750 mg) orally once a day]
Other Name: CPP-1X

Drug: Sulindac placebo
Sulindac placebo [one tablet orally once a day]

Active Comparator: Sulindac plus Eflornithine Placebo
Sulindac 150 mg and Placebo
Drug: Eflornithine Placebo
Eflornithine placebo [three tablets orally once a day]
Other Name: CPP-1X placebo

Drug: Sulindac 150 MG
Sulindac [one tablet orally once a day]
Other Name: Clinoril

Primary Outcome Measures :
  1. Delaying time to the 1st occurrence of any FAP-related event. [ Time Frame: Up to 48 months from the start of treatment ]
    time to progression of disease

Secondary Outcome Measures :
  1. improvement in investigator upper GI assessment [ Time Frame: month 6 and month 12 assessment ]
    global assessment of change in upper GI polyp burden

  2. improvement in investigator lower GI assessment [ Time Frame: month 6 and month 12 assessment ]
    global assessment of change in lower GI polyp burden

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01483144

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Sponsors and Collaborators
Cancer Prevention Pharmaceuticals, Inc.
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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
Additional Information:
Publications of Results:
Other Publications:
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Responsible Party: Cancer Prevention Pharmaceuticals, Inc. Identifier: NCT01483144    
Other Study ID Numbers: CPP-FAP-310
First Posted: December 1, 2011    Key Record Dates
Last Update Posted: March 24, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Cancer Prevention Pharmaceuticals, Inc.:
Familial Adenomatous Polyposis
Additional relevant MeSH terms:
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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
Antineoplastic Agents