Erlotinib Hydrochloride in Reducing Duodenal Polyp Burden in Patients With Familial Adenomatous Polyposis at Risk of Developing Colon Cancer

NCT02961374 | Completed Phase 2 Results DMC FDA Drug

• 5 other identifiers: NCI-2016-01674N01-CN-2012-00042MAY2016-07-01N01CN00042P30CA015083
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 8

Brief Summary

This phase II trial studies the side effects of erlotinib hydrochloride and how well it works in reducing duodenal polyp burden in patients with familial adenomatous polyposis at risk of developing colon cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Attenuated Familial Adenomatous Polyposis; Familial Adenomatous Polyposis

Outcome Measures

Primary Outcomes (2)

• Mean Percent Change in Duodenal Polyp Burden

  Assessed by esophagogastroduodenoscopy, the mean percent change was calculated by subtracting the sum of diameters from all polyps at baseline from the sum of diameters of all polyps at 6 months, then dividing by the sum of diameters from all polyps at baseline and multiplying by 100.

  Baseline to 6 months post-intervention

• Number of Participants With Grade 2/3 Adverse Event (AE)

  Assessed according to National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of patients reporting a grade 2 or higher event are reported.

  Up to 7 months from registration

Secondary Outcomes (7)

• Number of Participants With Any Adverse Events

  Up to 7 months from registration

• Change in Duodenal Polyp Number

  Baseline to 6 months

• Absolute Change in Lower Gastrointestinal Polyp Burden

  Baseline to 6 months

• Percent Change in Lower Gastrointestinal Polyp Burden

  Baseline to 6 months

• Absolute Change in Lower Gastrointestinal Polyp Number

  Baseline to 6 months

Other Outcomes (3)

• Immune Response Signaling in Duodenal Adenomas and Uninvolved Tissue

  Up to 2.5 years

• EGFR and Wnt Gene Expression

  Up to 2.5 years

• Change in Differentially Expressed Genes of Duodenal Polyps and Uninvolved Tissue

  Baseline to 2.5 years

Study Arms (1)

Treatment (erlotinib hydrochloride)

EXPERIMENTAL

Patients receive erlotinib hydrochloride PO once weekly. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.

Drug: Erlotinib; Drug: Erlotinib Hydrochloride

Interventions

Erlotinib DRUG

Given PO

Treatment (erlotinib hydrochloride)

Erlotinib Hydrochloride DRUG

Given PO

Also known as: Cp-358,774, OSI-774, Tarceva

Treatment (erlotinib hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of familial adenomatous polyposis (FAP) or attenuated familial adenomatous polyposis (AFAP), defined as at least one of the following:
• Genetic diagnosis with confirmed APC mutation (Clinical Laboratory Improvement Act \[CLIA\] certified lab or research testing)
• Obligate carrier
• Clinical diagnosis of classic FAP with \>= 100 colorectal adenomas status post colectomy and a family history of FAP
• Clinical diagnosis of FAP, based on personal and family history; Note: This criterion requires documented review and agreement from either the study chair or the Cancer Prevention Network (CPN) lead investigator
• Ability to understand and the willingness to sign a written informed consent document
• Willing to discontinue taking nonsteroidal anti-inflammatory drugs (NSAIDS) for 30 days prior to initiation of and during intervention; exception: use of =\< 81 mg daily or =\< 650 mg weekly aspirin is allowed
• Willing to discontinue smoking for the duration of study intervention
• Willing to provide mandatory biospecimens as specified in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Leukocytes (white blood cells \[WBC\]) \>= 3,000/uL (\>= 2,500/uL for African-American participants)
• Platelet count \>= 100 x 10\^9/L
• Hemoglobin \>= 11.5 g/dL
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
• Alkaline phosphatase =\< 1.5 x institutional upper limit of normal (ULN)

You may not qualify if:

• Any prior treatment with erlotinib or other agent whose primary mechanism of action is known to inhibit EGFR
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib
• Use of potent CYP3A4 inhibitors, including but not limited to ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice
• Use of potent CYP3A4 inducers, including but not limited to rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, and St. John's wort
• Use of any other investigational agents =\< 12 weeks prior to pre-registration
• Uncontrolled intercurrent illness or recent surgical procedure that in the opinion of the investigative team would limit compliance with study requirements, including, but not limited to:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Myocardial infarction =\< 6 months prior to intervention
• Severely impaired lung function
• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with study intervention
• Diagnosed liver disease, such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Puerto Rico

San Juan, 00936, Puerto Rico

Location

Related Publications (2)

• Stone JK, Mehta NA, Singh H, El-Matary W, Bernstein CN. Endoscopic and chemopreventive management of familial adenomatous polyposis syndrome. Fam Cancer. 2023 Oct;22(4):413-422. doi: 10.1007/s10689-023-00334-3. Epub 2023 Apr 29.

  PMID: 37119510 DERIVED

• Samadder NJ, Foster N, McMurray RP, Burke CA, Stoffel E, Kanth P, Das R, Cruz-Correa M, Vilar E, Mankaney G, Buttar N, Thirumurthi S, Turgeon DK, Sossenheimer M, Westover M, Richmond E, Umar A, Della'Zanna G, Rodriguez LM, Szabo E, Zahrieh D, Limburg PJ. Phase II trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis. Gut. 2023 Feb;72(2):256-263. doi: 10.1136/gutjnl-2021-326532. Epub 2022 May 30.

  PMID: 35636921 DERIVED

MeSH Terms

Conditions

Attenuated familial adenomatous polyposis; Adenomatous Polyposis Coli

Interventions

Erlotinib Hydrochloride

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

Results Point of Contact

• Title: Paul J. Limburg, M.D., M.P.H.
• Organization: Cancer Prevention Network (CPN) - Mayo Clinic College of Medicine

limburg.paul@mayo.edu

507-284-2511

Study Officials

• Niloy J Samadder

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2016
• First Posted: November 11, 2016
• Study Start: October 27, 2017
• Primary Completion: February 23, 2020
• Study Completion: September 27, 2021
• Last Updated: July 26, 2022
• Results First Posted: September 22, 2021

Record last verified: 2022-07

Locations

PR (1); US (7)