burt-neklason banner

Clinical Trials

Protocol Summary

Protocol No. 39278
Principal Investigator: Samadder, Jewel (Niloy)
Phase: II (Cancer Prevention)
Age Group: Adult
Secondary Protocol No. PPG- NIH Trial

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

Objective
This will be a single-center, phase-II, six-month-long, placebo-controlled, double blinded, randomized trial of the EGFR inhibitor erlotinib (Tarceva) and the COX 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 (endsosopy 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 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 pateints 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 and colorectal adenomas in FAP and attenuated FAP patients.

Secondary :

1. 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.

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

Key Eligibility
See attached PDF

Applicable Disease Sites: Genitourinary

Participating Institutions: Huntsman Cancer Institute

Status: Open

Other Attachments: Eligibility Criteria.pdf