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

NCT01483144 | Completed Phase 3 Results DMC

• 1 other identifier: CPP-FAP-310
• Study Type: interventional
• Target: 171
• Locations: 7 countries
• Sites: 17

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.

Conditions

Familial Adenomatous Polyposis

Keywords

Familial Adenomatous Polyposis; Eflornithine; Sulindac

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Any FAP-related Event.

  Progression of disease by evaluation of FAP-related events over the course of study treatment

  Up to 48 months from the start of treatment

Secondary Outcomes (2)

• Improvement in Investigator Upper GI Assessment

  through month 12 assessment

• Improvement in Investigator Lower GI Assessment

  through month 12 assessment

Study Arms (3)

Eflornithine plus Sulindac

EXPERIMENTAL

Eflornithine 750 mg and Sulindac 150 mg

Drug: Eflornithine; Drug: Sulindac 150 MG

Eflornithine plus Sulindac Placebo

ACTIVE COMPARATOR

Eflornithine 750 mg and Placebo

Drug: Eflornithine; Drug: Sulindac placebo

Sulindac plus Eflornithine Placebo

ACTIVE COMPARATOR

Sulindac 150 mg and Placebo

Drug: Eflornithine Placebo; Drug: Sulindac 150 MG

Interventions

Eflornithine DRUG

Eflornithine \[250 mg tablet, three tablets (750 mg) orally once a day\]

Also known as: CPP-1X

Eflornithine plus Sulindac; Eflornithine plus Sulindac Placebo

Eflornithine Placebo DRUG

Eflornithine placebo \[three tablets orally once a day\]

Also known as: CPP-1X placebo

Sulindac plus Eflornithine Placebo

Sulindac 150 MG DRUG

Sulindac \[one tablet orally once a day\]

Also known as: Clinoril

Eflornithine plus Sulindac; Sulindac plus Eflornithine Placebo

Sulindac placebo DRUG

Sulindac placebo \[one tablet orally once a day\]

Eflornithine plus Sulindac Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of phenotypic classical FAP with disease involvement of the duodenum and/or colon/rectum/pouch.
• Genotype: Adenomatous polyposis coli (APC) mutation (with or without family history) required
• 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:
• 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. \[Note: For staging purposes only.\]
• 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:
• Current Spigelman Stage 3 or 4.
• 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):
• No significant hematologic abnormalities
• White blood cell count (WBC) at least 3,000/mm3

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cancer Prevention Pharmaceuticals, Inc.: lead

Study Sites (17)

University of California San Diego

La Jolla, California, 92093, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah- Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Zane Cohen Centre For Digestive Diseases

Toronto, Ontario, M5T 3L9, Canada

Location

University Hospital Bonn

Bonn, 53105, Germany

Location

Academic Medical Centre

Amsterdam, 1100 DE, Netherlands

Location

Institut de Malalties Digestives

Barcelona, Catalonia, 08036, Spain

Location

Institute of Genetic Medicine

Newcastle upon Tyne, Tyne and Wear, NEI 3BZ, United Kingdom

Location

Manchester Center for Genomic Medicine

Manchester, M13 NWL, United Kingdom

Location

Related Publications (3)

• Burke CA, Dekker E, Samadder NJ, Stoffel E, Cohen A. Efficacy and safety of eflornithine (CPP-1X)/sulindac combination therapy versus each as monotherapy in patients with familial adenomatous polyposis (FAP): design and rationale of a randomized, double-blind, Phase III trial. BMC Gastroenterol. 2016 Aug 2;16(1):87. doi: 10.1186/s12876-016-0494-4.

  PMID: 27480131 BACKGROUND

• Burke CA, Dekker E, Lynch P, Samadder NJ, Balaguer F, Huneburg R, Burn J, Castells A, Gallinger S, Lim R, Stoffel EM, Gupta S, Henderson A, Kallenberg FG, Kanth P, Roos VH, Ginsberg GG, Sinicrope FA, Strassburg CP, Van Cutsem E, Church J, Lalloo F, Willingham FF, Wise PE, Grady WM, Ford M, Weiss JM, Gryfe R, Rustgi AK, Syngal S, Cohen A. Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis. N Engl J Med. 2020 Sep 10;383(11):1028-1039. doi: 10.1056/NEJMoa1916063.

  PMID: 32905675 RESULT

• Balaguer F, Stoffel EM, Burke CA, Dekker E, Samadder NJ, Van Cutsem E, Lynch PM, Wise PE, Huneburg R, Lim RM, Boytim ML, Du W, Bruckheimer EM, Cohen A, Church J; FAP-310 Investigators. Combination of Sulindac and Eflornithine Delays the Need for Lower Gastrointestinal Surgery in Patients With Familial Adenomatous Polyposis: Post Hoc Analysis of a Randomized Clinical Trial. Dis Colon Rectum. 2022 Apr 1;65(4):536-545. doi: 10.1097/DCR.0000000000002095.

  PMID: 34261858 DERIVED

MeSH Terms

Conditions

Adenomatous Polyposis Coli

Interventions

Eflornithine; Sulindac

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Michelle Boytim
• Organization: Cancer Prevention Pharmaceuticals

mboytim@canprevent.com

520-908-7774

Study Officials

• Carol Burke, M.D.

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

• James Church, M.D.

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

• Gabriella Möslein, M.D.

  Helios Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2011
• First Posted: December 1, 2011
• Study Start: October 1, 2013
• Primary Completion: November 1, 2018
• Study Completion: March 1, 2019
• Last Updated: June 8, 2021
• Results First Posted: June 8, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); NL (1); BE (1); US (10); ES (1); DE (1); GB (2)