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

Information source: Cancer Prevention Pharmaceuticals, Inc.
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Familial Adenomatous Polyposis

Intervention: Eflornithine plus Sulindac (Drug); Eflornithine and Placebo (Drug); Sulindac and Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Cancer Prevention Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Carol Burke, M.D., Principal Investigator, Affiliation: The Cleveland Clinic
James Church, M.D., Principal Investigator, Affiliation: The Cleveland Clinic
Gabriella Möslein, M.D., Principal Investigator, Affiliation: Helios Hospital

Overall contact:
Alfred M Cohen, MD, Phone: 520-908-7774, Email: acohen@canprevent.com


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.

Clinical Details

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

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

Secondary outcome:

presence or absence of an ODC polymorphism

excretion of 4 urinary polyamines


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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


- 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


- 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.

Locations and Contacts

Alfred M Cohen, MD, Phone: 520-908-7774, Email: acohen@canprevent.com

University Hospital Bonn, Bonn 53105, Germany; Recruiting
Christian Strassburg, Prof, Principal Investigator
Gabriella Möslein, Prof Dr med, Sub-Investigator
Robert Hüneburg, Dr, Sub-Investigator

Academic Medical Centre, Amsterdam 1100 DE, Netherlands; Recruiting
Evelien Dekker, MD/PhD, Principal Investigator

Manchester Center for Genomic Medicine, Manchester M13 NWL, United Kingdom; Recruiting
Fiona Lalloo, MD, Principal Investigator

University of California San Diego, La Jolla, California 92093, United States; Recruiting
Allan Asuncion, Phone: 858-657-5169, Email: aasuncion@ucsd.edu
Samir Gupta, MD, Principal Investigator

Institut de Malalties Digestives, Barcelona, Catalonia 08036, Spain; Recruiting
Francesc Balaguer, Email: fprunes@clinic.ub.es
Antoni Castells, MD, Principal Investigator
Francesc Balaguer, MD, Sub-Investigator

Cleveland Clinic Florida, Weston, Florida 33331, United States; Recruiting
Giovanna da Silva, MD, Principal Investigator

Dana Farber Cancer Institute, Boston, Massachusetts 02215, United States; Recruiting
Victoriana Curry, Phone: 617-632-3354, Email: fapstudy@dfci.harvard.edu
Ramona Lim, M.D., Principal Investigator
Sapna Syngal, M.D., M.P.H., Sub-Investigator

University of Michigan, Ann Arbor, Michigan 48109, United States; Recruiting
Erika Koeppe, Phone: 734-998-1274, Email: eskoeppe@umich.edu
Elena Stoffel, M.D., M.P.H., Principal Investigator

Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Joni Noaeill, Phone: 507-284-9081, Email: Noaeill.joni@mayo.edu
Frank A. Sinicrope, M.D., Principal Investigator

Washington University, St. Louis, Missouri 63110, United States; Recruiting
Michelle Cusumano, RN, Phone: 314-362-2646, Email: cusumanom@wudosis.wustl.edu
Paul E. Wise, M.D., Principal Investigator

Cleveland Clinic, Cleveland, Ohio 44195, United States; Recruiting
Henrietta Hasson, Phone: 216-444-6975, Email: hassonh@ccf.org
Carol Burke, M.D., Principal Investigator
James Church, M.D., Principal Investigator

Zane Cohen Centre For Digestive Diseases, Toronto, Ontario M5T 3L9, Canada; Recruiting
Steve Gallinger, M.D., MSc, Principal Investigator
Robert Gryfe, M.D., Ph.D., Sub-Investigator
Zane Cohen, M.D., Sub-Investigator

University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States; Recruiting
Julie Starr, Phone: 215-349-8527, Email: jstarr@mail.med.upenn.edu
Anil Rustgi, MD, Principal Investigator

MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Gladis Shuttlesworth, PhD, Phone: 713-792-7470, Email: gashuttle@mdanderson.org
Tauseef Akhlaque, Phone: 713-792-2351, Email: takhlaque@mdanderson.org
Patrick M. Lynch, M.D., J.D., Principal Investigator

Institute of Genetic Medicine, Newcastle Upon Tyne, Tyne and Wear NEI 3BZ, United Kingdom; Recruiting
Alex Henderson, MD, Email: alex.henderson@nuth.nhs.uk
Alex Henderson, MD, Principal Investigator

University of Utah- Huntsman Cancer Institute, Salt Lake City, Utah 84112, United States; Recruiting
Michelle Done, Phone: 800-650-9071, Email: michelle.done@hci.utah.edu
Jewel Sammader, MD, Principal Investigator

University of Wisconsin, Madison, Wisconsin 53705, United States; Recruiting
Jenny Vue, Phone: 608-262-5404, Email: jxvue@medicine.wisc.edu
Jennifer Weiss, MD, Principal Investigator

Additional Information

Starting date: October 2013
Last updated: July 27, 2015

Page last updated: August 23, 2015

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