Phase II Trial of Weekly Erlotinib Dosing to Reduce Duodenal Polyp Burden Associated With Familial Adenomatous Polyposis
Overview
- Phase
- Phase 2
- Intervention
- Erlotinib
- Conditions
- Attenuated Familial Adenomatous Polyposis
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 46
- Locations
- 8
- Primary Endpoint
- Mean Percent Change in Duodenal Polyp Burden
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the mean percent change in duodenal polyp burden (sum of diameters from all polyps) from baseline to 6 months post-intervention for familial adenomatous polyposis (FAP) subjects receiving weekly erlotinib hydrochloride (erlotinib). II. To assess the grade 2/3 adverse event rate in this population and compare it to historical data. SECONDARY OBJECTIVES: I. To evaluate all adverse events at least possibly attributed to weekly erlotinib. II. To assess the absolute and percent change in duodenal polyp number from baseline to 6 months. III. To assess the absolute and percent changes in lower gastrointestinal polyp burden and number for the subset of participants with ileal pouch anal anastomosis (IPAA) or ileo-rectal anastomosis with rectal stump. IV. To assess the absolute and percent change in desmoid tumor size in participants who have baseline and follow up computed tomography (CT)s performed as part of their standard of care. CORRELATIVE OBJECTIVES: I. Gene expression profiles in duodenal adenomas and uninvolved tissue will be compared between baseline and endpoint samples using negative binomial statistics (DESeq2). II. Identify differentially expressed genes between duodenal polyps and uninvolved tissue at endpoint compared to baseline. III. Evaluate the effect of weekly erlotinib on EGFR and Wnt target gene expression in duodenal adenomas. IV. Evaluate the effect of weekly erlotinib on immune response signaling in duodenal adenomas and uninvolved tissue. OUTLINE: Patients receive erlotinib hydrochloride orally (PO) once weekly. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •PRE-REGISTRATION INCLUSION
- •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
Exclusion Criteria
- •PRE-REGISTRATION EXCLUSION
- •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
Arms & Interventions
Treatment (erlotinib hydrochloride)
Patients receive erlotinib hydrochloride PO once weekly. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
Intervention: Erlotinib
Treatment (erlotinib hydrochloride)
Patients receive erlotinib hydrochloride PO once weekly. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
Intervention: Erlotinib Hydrochloride
Outcomes
Primary Outcomes
Mean Percent Change in Duodenal Polyp Burden
Time Frame: Baseline to 6 months post-intervention
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.
Number of Participants With Grade 2/3 Adverse Event (AE)
Time Frame: Up to 7 months from registration
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.
Secondary Outcomes
- Absolute Change in Lower Gastrointestinal Polyp Burden(Baseline to 6 months)
- Percent Change in Lower Gastrointestinal Polyp Burden(Baseline to 6 months)
- Absolute and Percent Change in Desmoid Tumor Size(Baseline to 6 months)
- Absolute Change in Lower Gastrointestinal Polyp Number(Baseline to 6 months)
- Percent Change in Lower Gastrointestinal Polyp Number(Baseline to 6 months)
- Number of Participants With Any Adverse Events(Up to 7 months from registration)
- Change in Duodenal Polyp Number(Baseline to 6 months)