Clinical Trials /

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

NCT01483144

Description:

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.

Related Conditions:
  • Familial Adenomatous Polyposis
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Trial of <span class="go-doc-concept go-doc-intervention">Eflornithine Plus Sulindac</span> in Patients With Familial Adenomatous Polyposis (FAP)

Title

  • Brief Title: Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP)
  • 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
  • Clinical Trial IDs

    NCT ID: NCT01483144

    ORG ID: CPP-FAP-310

    Trial Conditions

    Familial Adenomatous Polyposis

    Trial Interventions

    Drug Synonyms Arms
    Eflornithine plus Sulindac Eflornithine plus Sulindac
    Eflornithine and Placebo Eflornithine plus Placebo
    Sulindac and Placebo Sulindac plus Placebo

    Trial Purpose

    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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Eflornithine plus Sulindac Experimental Eflornithine 750 mg and Sulindac 150 mg Eflornithine plus Sulindac
    Eflornithine plus Placebo Active Comparator Eflornithine 750 mg and Placebo Eflornithine and Placebo
    Sulindac plus Placebo Active Comparator Sulindac 150 mg and Placebo Sulindac and Placebo

    Eligibility Criteria

    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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Delaying time to the 1st occurrence of any FAP-related event.

    Secondary Outcome Measures

    presence or absence of an ODC polymorphism

    excretion of 4 urinary polyamines

    Trial Keywords

    Familial Adenomatous Polyposis

    Eflornithine

    Sulindac