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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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 (AFAP) patients.

Detailed Summary:

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 polyp burden at 6 mohths in FAP and attenuated FAP patients.

Secondary Aim: To measure if combination of sulindac and erlotinib cause a reduction in total duodenal polyp count, and change in duodenal polyp burden or count stratified by genotype and initial polyp burden.


Sponsor: University of Utah

Current Primary Outcome: Change in Duodenal Polyp Burden From Baseline to 6 Months [ Time Frame: Baseline and 6 months ]

A comparison between the Sulindac-erlotinib and Placebo arms of the change in polyp burden from a 10-centimeter segment of the duodenum, measured as the sum of the diameters of the polyps, in millimeters (mm), from the duodenal segment (6-month polyp burden minus baseline polyp burden).


Original Primary Outcome: Compare the change in total duodenal and colorectal polyp burden at 6 months [ Time Frame: Every 6 months ]

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.


Current Secondary Outcome:

  • Change in Duodenal Polyp Burden From Baseline to 6 Months in Classic Familial Adenomatous Polyposis (FAP) Participants [ Time Frame: Baseline and 6 months ]
    A comparison between the Sulindac-erlotinib and Placebo arm Classic FAP subgroups of the change in polyp burden from a 10-centimeter segment of the duodenum, measured as the sum of the diameters of the polyps, in millimeters (mm), from the duodenal segment (6-month polyp burden minus baseline polyp burden).
  • Change in Duodenal Polyp Burden From Baseline to 6 Months in Attenuated FAP Participants [ Time Frame: Baseline and 6 months ]
    A comparison between the Sulindac-erlotinib and Placebo arm Attenuated FAP subgroups of the change in polyp burden from a 10-centimeter segment of the duodenum, measured as the sum of the diameters of the polyps, in millimeters (mm), from the duodenal segment (6-month polyp burden minus baseline polyp burden).
  • Change in Number of Duodenal Polyps From Baseline to 6 Months [ Time Frame: Baseline and 6 months ]
    A comparison between the Sulindac-erlotinib and Placebo arms of the change in number of polyps in a 10-centimeter segment of the duodenum (6-month polyp count minus baseline polyp count).
  • Change in Number of Duodenal Polyps From Baseline to 6 Months in Classic FAP Participants [ Time Frame: Baseline and 6 months ]
    A comparison between the Sulindac-erlotinib and Placebo arm Classic FAP subgroups of the change in number of polyps in a 10-centimeter segment of the duodenum (6-month polyp count minus baseline polyp count)
  • Change in Number of Duodenal Polyps From Baseline to 6 Months in Attenuated FAP Participants [ Time Frame: Baseline and 6 months ]
    A comparison between the Sulindac-erlotinib and Placebo arm Attenuated FAP subgroups of the change in number of polyps in a 10-centimeter segment of the duodenum (6-month polyp count minus baseline polyp count)


Original Secondary Outcome:

Information By: University of Utah

Dates:
Date Received: August 3, 2010
Date Started: April 2010
Date Completion:
Last Updated: May 10, 2016
Last Verified: May 2016