Familial Adenomatous PolyposisPhase 3NCT01483144
Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP)
A Phase 3 study testing Eflornithine and Sulindac 150 MG in people with Familial Adenomatous Polyposis, run by Cancer Prevention Pharmaceuticals, Inc. at 17 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Familial Adenomatous Polyposis
- What is being tested?
- Eflornithine and Sulindac 150 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 171 participants
- Where
- 17 sitesin 7 countries
- Study dates
- Oct 2013to Mar 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
- Platelet count at least 100,000/mm3
- Hemoglobin at least 10.0 g/dL
- No history of clinical coagulopathy
- Hepatic Status (within 30 days prior to randomization):
- Bilirubin no greater than 1.5 times ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than 1.5 times ULN
- Alkaline phosphatase no greater than 1.5 times ULN
- Renal Status (within 30 days prior to randomization):
- Creatinine no greater than 1.5 times ULN
- Hearing:
- 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), dimethylsulfoxide (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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
17 sites in 7 countries.
17 sites in 7 countries
United States10 sites
University of Michigan
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30322
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Cleveland Clinic
Cleveland, Ohio, 44195
MD Anderson Cancer Center
Houston, Texas, 77030
University of California San Diego
La Jolla, California, 92093
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah- Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Washington University
St Louis, Missouri, 63110
United Kingdom2 sites
Manchester Center for Genomic Medicine
Manchester, M13 NWL
Institute of Genetic Medicine
Newcastle upon Tyne, Tyne and Wear, NEI 3BZ
Canada1 site
Zane Cohen Centre For Digestive Diseases
Toronto, Ontario, M5T 3L9
About this study
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
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
- Being tested
- Eflornithine, Eflornithine Placebo, Sulindac 150 MG, Sulindac placebo
- Keywords
- Familial Adenomatous Polyposis, Eflornithine, Sulindac
- Medical subject headings
- Adenomatous Polyposis Coli
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EflornithineDrug
Also called CPP-1X
Eflornithine [250 mg tablet, three tablets (750 mg) orally once a day]
Eflornithine PlaceboDrug
Also called CPP-1X placebo
Eflornithine placebo [three tablets orally once a day]
Sulindac 150 MGDrug
Also called Clinoril
Sulindac [one tablet orally once a day]
Sulindac placeboDrug
Sulindac placebo [one tablet orally once a day]
| Study group | Role | What they receive |
|---|---|---|
| Eflornithine plus Sulindac | Experimental | Eflornithine 750 mg and Sulindac 150 mg Receives: Drug: Eflornithine; Drug: Sulindac 150 MG |
| Eflornithine plus Sulindac Placebo | Active comparator | Eflornithine 750 mg and Placebo Receives: Drug: Eflornithine; Drug: Sulindac placebo |
| Sulindac plus Eflornithine Placebo | Active comparator | Sulindac 150 mg and Placebo Receives: Drug: Eflornithine Placebo; Drug: Sulindac 150 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Any FAP-related Event.
Progression of disease by evaluation of FAP-related events over the course of study treatment
Measured: Up to 48 months from the start of treatment
Secondary outcomes (2)
Improvement in Investigator Upper GI Assessment
Global assessment of change in upper GI polyp burden. These are binary outcomes derived from scores assigned by the investigator during each procedure, using a scale (-2, -1, 0, +1, +2) which corresponds, respectively, to the investigator's overall qualitative assessment of: much worse, worse, no change, improved, much improved. Summarizes the corresponding 6- and 12-month investigator change scores according to whether or not there was any positive improvement at either month 6 (compared to baseline) or at month 12 (compared to baseline or month 6), under the condition that there be no worsening at either timepoint.
Measured: through month 12 assessment
Improvement in Investigator Lower GI Assessment
Global assessment of change in lower GI polyp burden. These are binary outcomes derived from scores assigned by the investigator during each procedure, using a scale (-2, -1, 0, +1, +2) which corresponds, respectively, to the investigator's overall qualitative assessment of: much worse, worse, no change, improved, much improved. Summarizes the corresponding 6- and 12-month investigator change scores according to whether or not there was any positive improvement at either month 6 (compared to baseline) or at month 12 (compared to baseline or month 6), under the condition that there be no worsening at either timepoint.
Measured: through month 12 assessment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2011 (estimated)
- Study startOct 2013
- Primary completionNov 2018
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Familial Adenomatous PolyposisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Prevention Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Carol Burke, M.D., Principal investigator, The Cleveland ClinicJames Church, M.D., Principal investigator, The Cleveland ClinicGabriella Möslein, M.D., Principal investigator, Helios Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01483144
- Sponsor's protocol ID
- CPP-FAP-310
- Status last verified
- May 2021
- First submitted
- 21 Nov 2011
- Last updated
- 8 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 27480131Burke 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.
PubMed 32905675Balaguer 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.
PubMed 34261858
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01483144
- Acronym / sponsor ID
- CPP-FAP-310
- Conditions
- Familial Adenomatous Polyposis
- Keywords
- Familial Adenomatous Polyposis, Eflornithine, Sulindac
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 171 participants (actual)
- Lead sponsor
- Cancer Prevention Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- Nov 2018 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 1 Dec 2011 (estimated)
- Results
- Posted 8 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Eflornithine plus Sulindac | Experimental | Drug: Eflornithine, Drug: Sulindac 150 MGEflornithine 750 mg and Sulindac 150 mg |
| Eflornithine plus Sulindac Placebo | Active comparator | Drug: Eflornithine, Drug: Sulindac placeboEflornithine 750 mg and Placebo |
| Sulindac plus Eflornithine Placebo | Active comparator | Drug: Eflornithine Placebo, Drug: Sulindac 150 MGSulindac 150 mg and Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- Diagnosis of phenotypic classical FAP with disease involvement of the duodenum and/or colon/rectum/pouch.
- 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:
- 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.]
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EflornithineAlso: CPP-1XEflornithine [250 mg tablet, three tablets (750 mg) orally once a day] | Drug | Eflornithine plus Sulindac, Eflornithine plus Sulindac Placebo |
| Eflornithine PlaceboAlso: CPP-1X placeboEflornithine placebo [three tablets orally once a day] | Drug | Sulindac plus Eflornithine Placebo |
| Sulindac 150 MGAlso: ClinorilSulindac [one tablet orally once a day] | Drug | Eflornithine plus Sulindac, Sulindac plus Eflornithine Placebo |
| Sulindac placeboSulindac placebo [one tablet orally once a day] | Drug | Eflornithine plus Sulindac Placebo |
Primary outcome
Number of Subjects With Any FAP-related Event.
Time frame: Up to 48 months from the start of treatment
Progression of disease by evaluation of FAP-related events over the course of study treatment
2 secondary outcomes
Improvement in Investigator Upper GI Assessment
Time frame: through month 12 assessment
Improvement in Investigator Lower GI Assessment
Time frame: through month 12 assessment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27480131Burke 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.
- Results publication: PubMed 32905675Burke 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.
- Derived from this study: PubMed 34261858Balaguer 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carol Burke, M.D. principal investigator
The Cleveland Clinic
James Church, M.D. principal investigator
The Cleveland Clinic
Gabriella Möslein, M.D. principal investigator
Helios Hospital
17 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eflornithine and Sulindac 150 MG in people with Familial Adenomatous Polyposis, run by Cancer Prevention Pharmaceuticals, Inc. at 17 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, United Kingdom, Belgium, Canada, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Any FAP-related Event. (time frame: Up to 48 months from the start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01483144, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2021.