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

May 10, 2016 updated by: Jewel Samadder, University of Utah

Genetic Events Leading to APC-Dependent Colon Cancer in High-Risk Families; a Clinical Trial of COX and EGFR Inhibition in Familial Polyposis Patients

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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 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.

Study Type

Interventional

Enrollment (Actual)

92

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 67 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients who are 18 years or older with a clinical or genetic diagnosis of FAP or attenuated FAP.
  • Presence of duodenal polyps with a sum of diameters ≥ 5mm.
  • Minimum of two weeks since any major surgery
  • WHO performance status ≤1
  • Adequate bone marrow function as show by: normal leukocyte count, platelet count ≥ 120 x 109/L, Hgb > 12 g/dL
  • Adequate liver function as shown by: normal serum bilirubin(≤ 1.5 Upper Limit Normal {ULN}) and serum transaminases (≤ 2.0 ULN)
  • Patient must discontinue taking any Nonsteroidal anti-inflammatory drugs (NSAIDS) within one month of treatment initiation.
  • Patients must be able to provide written informed consent.

Exclusion Criteria:

  • Prior treatment with any investigational drug within the preceding 4 weeks.
  • Malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skins.

  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study as determined by the Principal Investigator such as:

    1. Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia
    2. Severely impaired lung function
    3. Any active (acute or chronic) or uncontrolled infection/ disorders.
    4. Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
    5. Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis

  • Screening clinical laboratory values that indicate any of the following:

    1. anemia
    2. thrombocytopenia
    3. leucopenia
    4. elevations of transaminases greater than 2X ULN
    5. elevation of bilirubin > 1.5 X ULN
    6. alkaline phosphatase elevation > 1.5 X ULN
    7. increased creatinine, urinary protein, or urinary casts outside the clinically normal range.
  • Gastrointestinal bleeding (symptoms including dyspnea, fatigue, angina, weakness, malaise, melena, hematochezia, hematemesis, anemia or abdominal pain will require clinical assessment to rule out gastrointestinal bleeding).
  • Patient who is currently taking any anti-coagulation medication.
  • Women who are pregnant or breast feeding.
  • Patients with a known hypersensitivity to sulindac or erlotinib or to their excipients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Erlotinib and Sulindac
Erlotinib 75 mg per day in combination with sulindac 150 mg twice daily for 6 months.
Drug: Erlotinib
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 Names:
  • 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 Names:
  • Sulindac (ANDA#071891)
Placebo Comparator: Placebo A and Placebo B
Placebo capsules matching erlotinib active comparator (Placebo A) once daily and placebo capsules matching sulindac active comparator (Placebo B) twice daily for 6 months
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 Names:
  • Erlotinib placebo
Drug: 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 Names:
  • Sulindac placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Baseline and 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Baseline and 6 months
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).
Baseline and 6 months
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).
Baseline and 6 months
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)
Baseline and 6 months
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)
Baseline and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Utah

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Randall Burt, MD, University of Utah at Huntsman Cancer Institute
  • Principal Investigator: Niloy J Samadder, MD, University of Utah at Huntsman Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Actual)

June 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

August 3, 2010

First Submitted That Met QC Criteria

August 23, 2010

First Posted (Estimate)

August 24, 2010

Study Record Updates

Last Update Posted (Estimate)

June 17, 2016

Last Update Submitted That Met QC Criteria

May 10, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 00039278
  • P01CA073992 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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