An Investigational Drug (TPST-1495) in Patients With Familial Adenomatous Polyposis
NCT Number: NCT06557733
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Familial Adenomatous Polyposis
Interventions: PROCEDURE: Biopsy|PROCEDURE: Biospecimen Collection|DRUG: EP2/EP4 Antagonist TPST-1495|PROCEDURE: Esophagogastroduodenoscopy|PROCEDURE: Gastrointestinal Endoscopy|OTHER: Questionnaire Administration
Sponsor: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 38
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: PREVENTION
Start Date: 2025-02-04
Completion Date: 2026-12-17
Locations: Mayo Clinic Hospital in Arizona, Phoenix, Arizona, 85054, United States|Mayo Clinic in Rochester, Rochester, Minnesota, 55905, United States|Huntsman Cancer Institute/University of Utah, Salt Lake City, Utah, 84112, United States|University of Wisconsin Carbone Cancer Center - University Hospital, Madison, Wisconsin, 53792, United States|University of Puerto Rico, San Juan, 00936, Puerto Rico

Summary:
This open-label phase II trial tests how well TPST-1495 works in reducing the number of polyps in the small bowel and colon in patients with familial adenomatous polyposis (FAP). FAP is an inherited condition in which numerous polyps (growths that protrude from mucous membranes) form on the inside walls of the colon and rectum. It increases the risk for colon cancer. TPST-1495 binds to specific prostaglandin receptors. TPST-1495 is a dual antagonist of the prostaglandin E2 (PGE2) receptor subtypes EP2 and EP4, while sparing the immune-stimulating EP1 and EP3 receptors. TPST-1495 may help reduce the number of polyps in the small bowel and colon in patients with FAP.

Primary Outcome Measures: Percent change in duodenal polyp burden, Will be determined based on the sum of diameters from all polyps. Will be assessed by comparing upper gastrointestinal (GI) endoscopies respectively. Will be described using a two-sided 95% confidence interval and examined for difference from zero with a one-side paired t-test., Baseline to 6 months|Incidence of adverse events, Will examine the proportion of patients with grade 2 or 3 adverse events according to the Common Terminology Criteria for Adverse Events version 5.0. Will be summarized as a proportion with a 1-sided 90% confidence interval., Up to 7 months
Secondary Outcome Measures: Percent change in rectal/pouch polyp burden, Will be assessed by comparing the lower GI endoscopies. Results will be presented using summary statistics and corresponding confidence intervals., Baseline to 6 months
Other Outcome Measures: Percent change in immunohistochemical staining levels, Will assess rectal and duodenal tissue samples for COX-2 expression level, beta-catenin, and Ki-67. Mean percent change in immunohistochemical staining levels will be associated with intestinal polyp burden using a scatterplot of the two variables and evaluated using a Spearman rank correlation statistic., Baseline to 6 months|Proteomic profile, Will identify proteins that are statistically significantly differently expressed between patients after treatment. The proteomic profile of serum will be correlated to clinical response to therapy and compared between baseline and end of intervention. No formal statistical inference will be performed. Proteins will be described with summary statistics to assist in planning follow-up studies., Baseline to 6 months|TPST-1495 plasma concentrations, Will assess steady-state pharmacokinetics., At pre-dose and 2-and 4-hours post-dose at 3 months visit