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

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jewel Samadder, University of Utah
ClinicalTrials.gov Identifier:
First received: August 3, 2010
Last updated: June 20, 2014
Last verified: June 2014
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.

Condition Intervention Phase
Adenomatous Polyposis Coli
Drug: Erlotinib
Drug: Sulindac
Drug: Placebo A
Drug: Placebo B
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by University of Utah:

Primary Outcome Measures:
  • 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.

Estimated Enrollment: 100
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)
Arms Assigned Interventions
Active Comparator: erlotinib and sulindac
Erlotinib in combination with sulindac will be used in this arm of the study.
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 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 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 Name: Sulindac placebo

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 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.

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 Principle 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01187901

United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
National Cancer Institute (NCI)
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
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jewel Samadder, Principle Investigator, University of Utah
ClinicalTrials.gov Identifier: NCT01187901     History of Changes
Other Study ID Numbers: 00039278  P01CA073992 
Study First Received: August 3, 2010
Last Updated: June 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Utah:
Familial Adenomatous Polyposis
Attenuated Familial Polyposis

Additional relevant MeSH terms:
Adenomatous Polyposis Coli
Adenomatous Polyps
Colonic Diseases
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Genetic Diseases, Inborn
Intestinal Diseases
Intestinal Neoplasms
Intestinal Polyposis
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplastic Syndromes, Hereditary
Erlotinib Hydrochloride
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on May 26, 2016