Title |
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
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Published in |
BMC Gastroenterology, August 2016
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DOI | 10.1186/s12876-016-0494-4 |
Pubmed ID | |
Authors |
Carol A. Burke, Evelien Dekker, N. Jewel Samadder, Elena Stoffel, Alfred Cohen |
Abstract |
Molecular studies suggest inhibition of colorectal mucosal polyamines (PAs) may be a promising approach to prevent colorectal cancer (CRC). Inhibition of ornithine decarboxylase (ODC) using low-dose eflornithine (DFMO, CPP-1X), combined with maximal PA export using low-dose sulindac, results in greatly reduced levels of normal mucosal PAs. In a clinical trial, this combination (compared with placebo) reduced the 3-year incidence of subsequent high-risk adenomas by >90 %. Familial Adenomatous Polyposis (FAP) is characterized by marked up-regulation of ODC in normal intestinal epithelial and adenoma tissue, and therefore PA reduction might be a potential strategy to control progression of FAP-related intestinal polyposis. CPP FAP-310, a randomized, double-blind, Phase III trial was designed to examine the safety and efficacy of sulindac and DFMO (alone or in combination) for preventing a clinically relevant FAP-related progression event in individuals with FAP. Eligible adults with FAP will be randomized to: CPP-1X 750 mg and sulindac 150 mg, CPP-1X placebo and sulindac 150 mg, or CPP-1X 750 mg and sulindac placebo once daily for 24 months. Patients will be stratified based on time-to-event prognosis into one of the three treatment arms: best (ie, longest time to first FAP-related event [rectal/pouch polyposis]), intermediate (duodenal polyposis) and worst (pre-colectomy). Stage-specific, "delayed time to" FAP-related events are the primary endpoints. Change in polyp burden (upper and/or lower intestine) is a key secondary endpoint. The trial is ongoing. As of February 1, 2016, 214 individuals have been screened; 138 eligible subjects have been randomized to three treatment groups at 15 North American sites and 6 European sites. By disease strata, 26, 80 and 32 patients are included for assessment of polyp burden in the rectum/pouch, duodenal polyposis and pre-colectomy groups, respectively. Median age is 40 years; 59 % are men. The most common reasons for screening failure include minimal polyp burden (n = 22), withdrawal of consent (n = 9) and extensive polyposis requiring immediate surgical intervention (n = 9). Enrollment is ongoing. This trial is registered at ClinicalTrials.gov ( NCT01483144 ; November 21, 2011) and the EU Clinical Trials Register( EudraCT 2012-000427-41 ; May 15, 2014). |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 88 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 12 | 14% |
Student > Master | 12 | 14% |
Student > Bachelor | 10 | 11% |
Student > Ph. D. Student | 9 | 10% |
Other | 8 | 9% |
Other | 17 | 19% |
Unknown | 20 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 32 | 36% |
Biochemistry, Genetics and Molecular Biology | 7 | 8% |
Nursing and Health Professions | 7 | 8% |
Agricultural and Biological Sciences | 5 | 6% |
Psychology | 5 | 6% |
Other | 11 | 13% |
Unknown | 21 | 24% |