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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
Given PO
Given PO
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
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.
Time frame: 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.
Time frame: Up to 7 months from registration
Number of Participants With Any Adverse Events
Assessed according to NCI CTCAE version 4.0. All registered and treated participants will be evaluable for AEs from the time of their first dose of weekly erlotinib treatment. To evaluate the AE profile for this treatment, the maximum grade for each type of adverse event will be recorded for each participant and frequency tables will be reviewed to determine the overall patterns. The number of patients reporting a grade 1 or higher adverse event at least possibly related to treatment are reported.
Time frame: Up to 7 months from registration
Change in Duodenal Polyp Number
The number of duodenal polyps at baseline and the number of polyps remaining after 6 months of treatment will collected. The change in duodenal polyp number will be calculated for each patient by subtracting the baseline number of polyps from the 6 month number. Therefore a negative value indicates a decrease in the number of polyps present after 6 months. The median difference and standard deviation is reported.
Time frame: Baseline to 6 months
Absolute Change in Lower Gastrointestinal Polyp Burden
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NONE
Enrollment
46
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
M D Anderson Cancer Center
Houston, Texas, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
University of Puerto Rico
San Juan, Puerto Rico
Lower GI polyp burden was defined using the Pouch Exam form as either 1) the average diameter reported for pouch for participants with ileal pouch-anal anastomosis (IPAA), or 2) the average diameter reported for rectum for participants with ileorectal anastomosis (IRA) + rectal stump. Absolute change from baseline to month 6 are reported here.
Time frame: Baseline to 6 months
Percent Change in Lower Gastrointestinal Polyp Burden
Lower GI polyp burden was defined using the Pouch Exam form as either 1) the average diameter reported for pouch for participants with ileal pouch-anal anastomosis (IPAA), or 2) the average diameter reported for rectum for participants with ileorectal anastomosis (IRA) + rectal stump. The percent change from baseline to month 6 are reported here.
Time frame: Baseline to 6 months
Absolute Change in Lower Gastrointestinal Polyp Number
Lower GI polyp number was defined using the Pouch Exam form as either 1) the number of polyps reported for pouch for participants with ileal pouch-anal anastomosis (IPAA), or 2) the number of polyps reported for rectum for participants with ileorectal anastomosis (IRA) + rectal stump. Absolute change from baseline to month 6 are reported here.
Time frame: Baseline to 6 months
Percent Change in Lower Gastrointestinal Polyp Number
Lower GI polyp number was defined using the Pouch Exam form as either 1) the number of polyps reported for pouch for participants with IPAA, or 2) the number of polyps reported for rectum for participants with IRA + rectal stump.
Time frame: Baseline to 6 months
Absolute and Percent Change in Desmoid Tumor Size
Laboratory measures will be correlated with participant outcomes (i.e., polyp burden, adverse events) and with each other as well. Cut-points will be determined based on previously defined and accepted standards. Descriptive statistics and simple scatter plots will be generated to review the tissue-based biomarker data. For continuous variables, the actual and % change in the level of each of the biomarkers from pre- to post-intervention will be explored using Wilcoxon signed rank tests, and paired sample t-tests. All categorical variables will be analyzed using chi-square tests or Fisher's exact test. For all translational endpoints, any notable statistical result will be viewed as an impetus for further study rather than as a definitive finding in and of itself.
Time frame: Baseline to 6 months