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

NCT01187901 | Completed Phase 2 Results DMC

• 2 other identifiers: 00039278P01CA073992
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

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.

Conditions

Adenomatous Polyposis Coli

Keywords

Familial Adenomatous Polyposis; Attenuated Familial Polyposis

Outcome Measures

Primary Outcomes (1)

• Change in Duodenal Polyp Burden From Baseline to 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 Outcomes (5)

• Change in Duodenal Polyp Burden From Baseline to 6 Months in Classic Familial Adenomatous Polyposis (FAP) Participants

  Baseline and 6 months

• Change in Duodenal Polyp Burden From Baseline to 6 Months in Attenuated FAP Participants

  Baseline and 6 months

• Change in Number of Duodenal Polyps From Baseline to 6 Months

  Baseline and 6 months

• Change in Number of Duodenal Polyps From Baseline to 6 Months in Classic FAP Participants

  Baseline and 6 months

• Change in Number of Duodenal Polyps From Baseline to 6 Months in Attenuated FAP Participants

  Baseline and 6 months

Study Arms (2)

Erlotinib and Sulindac

ACTIVE COMPARATOR

Erlotinib 75 mg per day in combination with sulindac 150 mg twice daily for 6 months.

Drug: Erlotinib; Drug: Sulindac

Placebo A and Placebo B

PLACEBO COMPARATOR

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; Drug: Placebo B

Interventions

Erlotinib DRUG

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.

Also known as: Tarceva (NDA#021743)

Erlotinib and Sulindac

Sulindac DRUG

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

Also known as: Sulindac (ANDA#071891)

Erlotinib and Sulindac

Placebo A DRUG

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.

Also known as: Erlotinib placebo

Placebo A and Placebo B

Placebo B DRUG

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).

Also known as: Sulindac placebo

Placebo A and Placebo B

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia
• Severely impaired lung function
• Any active (acute or chronic) or uncontrolled infection/ disorders.
• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
• Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• Screening clinical laboratory values that indicate any of the following:
• anemia
• thrombocytopenia
• leucopenia
• elevations of transaminases greater than 2X ULN
• elevation of bilirubin \> 1.5 X ULN
• alkaline phosphatase elevation \> 1.5 X ULN

Sponsors & Collaborators

• University of Utah: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (3)

• Sample DC, Samadder NJ, Pappas LM, Boucher KM, Samowitz WS, Berry T, Westover M, Nathan D, Kanth P, Byrne KR, Burt RW, Neklason DW. Variables affecting penetrance of gastric and duodenal phenotype in familial adenomatous polyposis patients. BMC Gastroenterol. 2018 Jul 16;18(1):115. doi: 10.1186/s12876-018-0841-8.

  PMID: 30012100 DERIVED

• Samadder NJ, Kuwada SK, Boucher KM, Byrne K, Kanth P, Samowitz W, Jones D, Tavtigian SV, Westover M, Berry T, Jasperson K, Pappas L, Smith L, Sample D, Burt RW, Neklason DW. Association of Sulindac and Erlotinib vs Placebo With Colorectal Neoplasia in Familial Adenomatous Polyposis: Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2018 May 1;4(5):671-677. doi: 10.1001/jamaoncol.2017.5431.

  PMID: 29423501 DERIVED

• Samadder NJ, Neklason DW, Boucher KM, Byrne KR, Kanth P, Samowitz W, Jones D, Tavtigian SV, Done MW, Berry T, Jasperson K, Pappas L, Smith L, Sample D, Davis R, Topham MK, Lynch P, Strait E, McKinnon W, Burt RW, Kuwada SK. Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial. JAMA. 2016 Mar 22-29;315(12):1266-75. doi: 10.1001/jama.2016.2522.

  PMID: 27002448 DERIVED

MeSH Terms

Conditions

Adenomatous Polyposis Coli

Interventions

Erlotinib Hydrochloride; Sulindac

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: N. Jewel Samadder
• Organization: University of Utah

jewel.samadder@hsc.utah.edu

801-213-4211

Study Officials

• Randall Burt, MD

  University of Utah at Huntsman Cancer Institute

  STUDY CHAIR

• Niloy J Samadder, MD

  University of Utah at Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 3, 2010
• First Posted: August 24, 2010
• Study Start: April 1, 2010
• Primary Completion: June 1, 2014
• Study Completion: July 1, 2014
• Last Updated: June 17, 2016
• Results First Posted: June 17, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)