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A Trial of Low Dose Sulindac Combined With Eflornithine in Patients With Familial Adenomatous Polyposis (FAP)

Primary Purpose

Familial Adenomatous Polyposis

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Eflornithine plus Sulindac
Eflornithine plus Placebo
Sulindac plus Placebo
Sponsored by
Cancer Prevention Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Familial Adenomatous Polyposis focused on measuring colon polyps

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of phenotypic Familial Adenomatous Polyposis (FAP) of the colorectum based on meeting the criteria in one of two groups: Group 1-Greater than 100 adenomatous colorectal polyps prior to age 40. Group 2-Greater than 10 adenomatous polyps and age <40 or greater than 25 polyps and age >40; combined with a dominant family history or genotype: More than 100 polyps in a first-degree relative; More than 25 polyps in 2 relatives in 2 generations, including a first-degree family member; Genetic diagnosis in a relative; Genetic diagnosis by in vitro synthesized truncated protein or similar assay.
  • No colorectal surgery or prior colon surgery for polyposis at least 1 year prior (total abdominal colectomy with ileal-rectal anastomosis, or total proctocolectomy with ilea pouch-anal reconstruction.
  • Baseline endoscopy

    1. If no prior colorectal surgery, at least 3 polyps in a cluster each ≥ 2 mm in diameter; or
    2. If rectum is in situ and to be assessed, baseline rectal segment endoscopy documenting 3 or more rectal polyps each at least 2 mm in diameter in a defined cluster and/or at least 6 polyps, ≥ 2 mm in diameter, in the distal 10 cm of rectum
    3. If ileal pouch neo-rectum is in place, 3 or more pouch polyps in a cluster ≥ 2 mm in diameter, or at least 6 polyps, ≥ 2 mm in diameter, in the distal 10 cm of pouch.
    4. Clinical/pathological grading of duodenal polyps will utilize the Spigelman Classification.
  • Hematopoietic: no significant hematologic dysfunction; WBC ≥3,000/mm3; platelet count ≥100,000/mm3; hemoglobin ≥10g/dL; no known or prior clinical coagulopathy.
  • Hepatic: bilirubin ≤ 1.5 times ULN; AST and ALT ≤ 1.5 times ULN; Alkaline phosphatase ≤ 1.5 times ULN.
  • Renal: No significant renal dysfunction; creatinine ≤ 1.5 times ULN.
  • Hearing: no clinically significant hearing loss that affects everyday life.
  • Not pregnant or nursing.
  • Negative serum pregnancy test if female of child-bearing potential.
  • Absence of gross blood in stool.
  • Fertile patients must use effective contraception.
  • Stool occult blood either negative or minimal (1+).
  • No prior hypersensitivity to cyclooxygenase-2 inhibitors, sulfonamides, NSAIDs, or salicylates; no NSAID associated symptoms of gastritis.
  • No discrete gastric or duodenal ulcer greater than 5 mm within the past year except Helicobacter pylori-related peptic ulcer disease treated successfully with antibiotics (as documented by an endoscopy.
  • No invasive malignancy within the past 5 years except stage I or II colon or rectal cancer or resected nonmelanomatous skin cancer.
  • No other significant medical or psychiatric problems that would preclude study participation.
  • No chronic adrenocorticosteroids.
  • No prior pelvic irradiation.
  • At least 3 months since prior investigational agents.
  • Patients may not be receiving or plan to receive corticosteroids.
  • Concomitant NSAID use outside this study may not exceed 4 days per month.
  • Use of 81 mg daily aspirin or 650 mg aspirin not more than once a week.
  • No concurrent warfarin, fluconazole, or lithium.
  • Must be willing and able to sign informed consent.

Exclusion Criteria:

  • High Risk for cardiovascular disease including clinical diabetes mellitus (Type I or II) requiring glycemic medications; Prior personal history of cardiovascular disease or, two or more of the following - hypertension or use of anti-hypertensive medications, hyperlipidemia or use of lipid-lowering medications or current smoker.
  • Hearing loss that affects everyday life and or for which a hearing aid is required.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Active Comparator

    Active Comparator

    Arm Label

    Eflornithine plus Sulindac

    Elfornithine plus Placebo

    Sulindac plus Placebo

    Arm Description

    Eflornithine 500 mg and Sulindac 150 mg

    Eflornithine 500 mg and Placebo

    Sulindac 150 mg and Placebo

    Outcomes

    Primary Outcome Measures

    Efficacy of Eflornithine plus Sulindac compared to Eflornithine alone and Sulindac alone determined by change in the number of polyps 2 mm or greater in a defined focal area of the rectum or pouch at baseline and after completion of the study treatment.

    Secondary Outcome Measures

    Change in number of polyps 2 mm or greater in the distal 10 cm of rectum or pouch.
    Qualitative change in overall colon/rectum/pouch polyp burden (number and size).
    Presence of high grade dysplasia or villous adenoma in any polyp resected.

    Full Information

    First Posted
    November 19, 2010
    Last Updated
    April 23, 2015
    Sponsor
    Cancer Prevention Pharmaceuticals, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01245816
    Brief Title
    A Trial of Low Dose Sulindac Combined With Eflornithine in Patients With Familial Adenomatous Polyposis (FAP)
    Official Title
    A Randomized Phase III Trial of Low Dose Sulindac Combined With Eflornithine in Patients With Familial Adenomatous Polyposis (FAP)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2015
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    March 2011 (undefined)
    Primary Completion Date
    May 2013 (Anticipated)
    Study Completion Date
    June 2013 (Anticipated)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Cancer Prevention Pharmaceuticals, Inc.

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this phase III study is to evaluate the safety and efficacy of the combination of eflornithine and sulindac compared to single agent sulindac or eflornithine in reducing the number of polyps in patients with familial adenomatous polyposis (FAP).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Familial Adenomatous Polyposis
    Keywords
    colon polyps

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Eflornithine plus Sulindac
    Arm Type
    Experimental
    Arm Description
    Eflornithine 500 mg and Sulindac 150 mg
    Arm Title
    Elfornithine plus Placebo
    Arm Type
    Active Comparator
    Arm Description
    Eflornithine 500 mg and Placebo
    Arm Title
    Sulindac plus Placebo
    Arm Type
    Active Comparator
    Arm Description
    Sulindac 150 mg and Placebo
    Intervention Type
    Drug
    Intervention Name(s)
    Eflornithine plus Sulindac
    Other Intervention Name(s)
    DFMO
    Intervention Description
    Eflornithine, 250 mg tablet, two tablets (500 mg) orally once a day; Sulindac, 150 mg tablet, one tablet orally once a day
    Intervention Type
    Drug
    Intervention Name(s)
    Eflornithine plus Placebo
    Other Intervention Name(s)
    DFMO
    Intervention Description
    Eflornithine, 250 mg tablet, two tablets (500 mg) orally once a day; Placebo, one tablet orally once a day
    Intervention Type
    Drug
    Intervention Name(s)
    Sulindac plus Placebo
    Intervention Description
    Sulindac, 150 mg tablet, one tablet orally once a day; Placebo, two tablets orally once a day
    Primary Outcome Measure Information:
    Title
    Efficacy of Eflornithine plus Sulindac compared to Eflornithine alone and Sulindac alone determined by change in the number of polyps 2 mm or greater in a defined focal area of the rectum or pouch at baseline and after completion of the study treatment.
    Time Frame
    6 months from the start of treatment.
    Secondary Outcome Measure Information:
    Title
    Change in number of polyps 2 mm or greater in the distal 10 cm of rectum or pouch.
    Time Frame
    6 months from the start of treatment.
    Title
    Qualitative change in overall colon/rectum/pouch polyp burden (number and size).
    Time Frame
    6 months from the start of treatment.
    Title
    Presence of high grade dysplasia or villous adenoma in any polyp resected.
    Time Frame
    6 months from the start of treatment.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Diagnosis of phenotypic Familial Adenomatous Polyposis (FAP) of the colorectum based on meeting the criteria in one of two groups: Group 1-Greater than 100 adenomatous colorectal polyps prior to age 40. Group 2-Greater than 10 adenomatous polyps and age <40 or greater than 25 polyps and age >40; combined with a dominant family history or genotype: More than 100 polyps in a first-degree relative; More than 25 polyps in 2 relatives in 2 generations, including a first-degree family member; Genetic diagnosis in a relative; Genetic diagnosis by in vitro synthesized truncated protein or similar assay. No colorectal surgery or prior colon surgery for polyposis at least 1 year prior (total abdominal colectomy with ileal-rectal anastomosis, or total proctocolectomy with ilea pouch-anal reconstruction. Baseline endoscopy If no prior colorectal surgery, at least 3 polyps in a cluster each ≥ 2 mm in diameter; or If rectum is in situ and to be assessed, baseline rectal segment endoscopy documenting 3 or more rectal polyps each at least 2 mm in diameter in a defined cluster and/or at least 6 polyps, ≥ 2 mm in diameter, in the distal 10 cm of rectum If ileal pouch neo-rectum is in place, 3 or more pouch polyps in a cluster ≥ 2 mm in diameter, or at least 6 polyps, ≥ 2 mm in diameter, in the distal 10 cm of pouch. Clinical/pathological grading of duodenal polyps will utilize the Spigelman Classification. Hematopoietic: no significant hematologic dysfunction; WBC ≥3,000/mm3; platelet count ≥100,000/mm3; hemoglobin ≥10g/dL; no known or prior clinical coagulopathy. Hepatic: bilirubin ≤ 1.5 times ULN; AST and ALT ≤ 1.5 times ULN; Alkaline phosphatase ≤ 1.5 times ULN. Renal: No significant renal dysfunction; creatinine ≤ 1.5 times ULN. Hearing: no clinically significant hearing loss that affects everyday life. Not pregnant or nursing. Negative serum pregnancy test if female of child-bearing potential. Absence of gross blood in stool. Fertile patients must use effective contraception. Stool occult blood either negative or minimal (1+). No prior hypersensitivity to cyclooxygenase-2 inhibitors, sulfonamides, NSAIDs, or salicylates; no NSAID associated symptoms of gastritis. No discrete gastric or duodenal ulcer greater than 5 mm within the past year except Helicobacter pylori-related peptic ulcer disease treated successfully with antibiotics (as documented by an endoscopy. No invasive malignancy within the past 5 years except stage I or II colon or rectal cancer or resected nonmelanomatous skin cancer. No other significant medical or psychiatric problems that would preclude study participation. No chronic adrenocorticosteroids. No prior pelvic irradiation. At least 3 months since prior investigational agents. Patients may not be receiving or plan to receive corticosteroids. Concomitant NSAID use outside this study may not exceed 4 days per month. Use of 81 mg daily aspirin or 650 mg aspirin not more than once a week. No concurrent warfarin, fluconazole, or lithium. Must be willing and able to sign informed consent. Exclusion Criteria: High Risk for cardiovascular disease including clinical diabetes mellitus (Type I or II) requiring glycemic medications; Prior personal history of cardiovascular disease or, two or more of the following - hypertension or use of anti-hypertensive medications, hyperlipidemia or use of lipid-lowering medications or current smoker. Hearing loss that affects everyday life and or for which a hearing aid is required.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Alfred M. Cohen, M.D.
    Organizational Affiliation
    Cancer Prevention Pharmaceuticals, Inc.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    A Trial of Low Dose Sulindac Combined With Eflornithine in Patients With Familial Adenomatous Polyposis (FAP)

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