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Withdrawn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
About this trial
This is an interventional treatment trial for Familial Adenomatous Polyposis focused on measuring colon polyps
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.
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
NCT ID
NCT01245816
First Posted
November 19, 2010
Last Updated
April 23, 2015
Sponsor
Cancer Prevention Pharmaceuticals, Inc.
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)
We'll reach out to this number within 24 hrs