A Clinical Trial of COX and EGFR Inhibition in Familial Polyposis Patients — FAPEST  

Adenomatous Polyposis Coli Clinical Trial

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

Status Active, not recruiting

Clinical Trial Summary

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.

Clinical Trial Description

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.

Secondary :

1. Measure if combination of sulindac and erlotinib cause a reduction in duodenal polyposis based on Spigelman classification.

2. Determine if the combination of sulindac and erlotinib causes a significant regression of colorectal adenomas.

3. 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.

4. Determine ß-catenin localization in adenomatous intestinal polyps with or without oncogenic KRAS mutations. ;

Study Design

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

Related Conditions & MeSH terms

• Adenomatous Polyposis Coli

• NCT number: NCT01187901
• Study type: Interventional
• Source: University of Utah
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 2010
• Completion date: April 2015