A Clinical Trial of COX and EGFR Inhibition in Familial Polyposis Patients (FAPEST)
The purpose of this study is to determine in a randomized, placebo-controlled, phase II trial if the combination of sulindac and erlotinib causes a significant regression of duodenal and colorectal adenomas in familial adenomatous polyposis (FAP) and attenuated FAP patients.
Adenomatous Polyposis Coli
Drug: Placebo A
Drug: Placebo B
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
|Official Title:||Genetic Events Leading to APC-Dependent Colon Cancer in High-Risk Families; a Clinical Trial of COX and EGFR Inhibition in Familial Polyposis Patients|
- Compare the change in total duodenal and colorectal polyp burden at 6 months [ Time Frame: Every 6 months ] [ Designated as safety issue: No ]A comparison of the total polyp burden in the duodenum, measured as the change in the sum if the diameters of the polyps from the duodenal segment and a comparison of the change in the total colorectal polyp burden, measured as the change in the sum of the diameters of the colorectal polyps in subjects with an intact colon. At the end of the 6-month treatment period, all visible polyps will be counted, measured, and recorded as performed in the pretreatment endoscopies. The primary analysis will be via Wilcoxon (Mann-Whitney) tests comparing the sulindac + erlotinib and placebo arms.
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||April 2015|
|Estimated Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
Active Comparator: erlotinib and sulindac
Erlotinib in combination with sulindac will be used in this arm of the study.
Tarceva oral tablets are conventional, immediate-release tablets containing erlotinib as the hydrochloride salt. Erlotinib(75mg)will be taken once daily for six months in combination with sulindac.
Other Name: Tarceva (NDA#021743)Drug: Sulindac
Sulindac is a non-steroidal, anti-inflammatory indene derivative designed for the treatment of arthritic conditions. For this study, sulindac (150mg) will be taken twice daily in combination with erlotinib
Other Name: Sulindac (ANDA#071891)
|Placebo Comparator: Corn starch pill||
Drug: Placebo A
Erlotinib (Tarceva) will provide a 25 mg identical placebo. This will be provided by the Division of Cancer Prevention at the NIH who will receive the drug and placebo from the manufacturer, OSI/Genentech. Dosage for Placebo A will be 75 mg a day for 6 months.
Other Name: Erlotinib placeboDrug: Placebo B
Sulindac will be encapsulated in 150 mg doses along with an identical encapsulated Placebo B. One 150 mg capsules of Placebo B will be taken twice per day with meals (breakfast and supper).
Other Name: Sulindac placebo
This will be a single-center, phase-II, six-month-long, placebo-controlled, double blinded, randomized trial of the epidermal growth factor receptor (EGFR) inhibitor, erlotinib (Tarceva) and the cyclooxygenase (COX-2) inhibitor, sulindac in patients with familial adenomatous polyposis (FAP) or attenuated FAP. FAP is an autosomal dominant inherited colon cancer predisposition with a 100% risk of colon cancer in the absence of preventive care (endoscopy and surgery). Efficacious chemoprevention for duodenal adenomas is an unmet clinical need in FAP patients that would reduce the morbidity from duodenectomy and risk of duodenal adenocarcinoma. Currently the only Food and Drug Administration (FDA)-approved chemopreventive agent is celecoxib which results in a modest reduction of duodenal and colorectal polyps and is associated with cardiac toxicity at effective doses. If it can be shown that combinatorial inhibition of COX-2 and EGFR activity leads to successful regression in duodenal adenomatous polyps in FAP, it could be used as an effective chemopreventive regimen in FAP patients with duodenal adenomas or who have undergone surgical resection of duodenal adenomas or have many rectal adenomas. FAP and AFAP patients will be screened by endoscopy for presence of 5 or more duodenal polyps, then randomized to either A) erlotinib at 75 mg/day and sulindac at 150 mg/day or B) placebo for 6 months. The endpoint will be endoscopy at 6 months.
Primary Aim : To determine if the combination of sulindac and erlotinib causes a significant regression of duodenal adenomas in FAP and attenuated FAP patients.
- Measure if combination of sulindac and erlotinib cause a reduction in duodenal polyposis based on Spigelman classification.
- Determine if the combination of sulindac and erlotinib causes a significant regression of colorectal adenomas.
- Measure changes in COX-2 expression, EGFR phosphorylation, MEK1 phosphorylation, AKT phosphorylation, Ki-67 expression and/or cyclin D1 expression in intestinal polyps and normal intestinal mucosa with treatment.
- Determine ß-catenin localization in adenomatous intestinal polyps with or without oncogenic KRAS mutations.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01187901
|United States, Utah|
|Huntsman Cancer Institute|
|Salt Lake City, Utah, United States, 84112|
|Study Chair:||Randall Burt, MD||University of Utah at Huntsman Cancer Institute|
|Principal Investigator:||Niloy Jewel Samadder, MD||University of Utah at Huntsman Cancer Institute|