Recruiting
Phase 2

TPST-1495

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06557733

Conditions

Colorectal Carcinoma

Familial Adenomatous Polyposis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

EP2/EP4 Antagonist TPST-1495

Esophagogastroduodenoscopy

Gastrointestinal Endoscopy

Study Details

Brief 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.

Conditions

Colorectal Carcinoma

Familial Adenomatous Polyposis

Study ID

NCT06557733

Start date

Mar 31, 2026

Status verified date

Aug, 2026

Completion date

Jun 30, 2027

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Diagnosis of familial adenomatous polyposis (FAP), defined as at least one of the following:

  • Genetic diagnosis with confirmed APC mutation (clinical CLIA \[clinical laboratory improvement amendments\] certified lab or research testing)
  • Obligate carrier
  • Clinical diagnosis of classic FAP with ≥ 100 colorectal adenomas status post colectomy or a sub-total 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 MW consortium lead investigator
  • Previously underwent prophylactic colectomy or sub-total colectomy with IRA (ileo-rectal or ileo-colonic anastomosis) or IPAA at least 12 months before pre-registration evaluation and without ongoing surgical complication
  • Willing to discontinue taking non-steroidal anti-inflammatory drugs (NSAIDs) 5 days prior to initiation of study treatment and limit frequency of NSAID dosing during study treatment
  • Age ≥ 18. Because no dosing or adverse event (AE) data are currently available on the use of TPST-1495 in participants < 18 years of age, children and adolescents are excluded from this study but will be eligible for future pediatric trials, if applicable
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
  • Leukocytes (white blood count \[WBC\]) ≥ 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 normal (ULN) (unless patient has Gilbert's)
  • Alkaline phosphatase ≤ 1.5 x institutional ULN
  • Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) ≤ 2 x institutional ULN
  • Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) ≤ 2 x institutional ULN
  • Creatinine ≤ institutional ULN
  • Urinary testing results within institutional limits of normal or deemed clinically insignificant
  • Individuals on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible
  • Presence of Spigelman 2 or 3 duodenal polyposis stage assessed by endoscopy
  • Not pregnant: The effects of TPST-1495 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation or for 90 days after stopping study agent. Additionally, men should not donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study agent. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
  • Not currently breastfeeding
  • Ability to understand and the willingness to sign a written informed consent document
  • Helicobacter (H.) pylori negative confirmed with gastric biopsy (at time of screening EGD). If positive for H. pylori the patient can be offered full course of approved therapy with confirmation of eradication and re-assessment for trial participation with likely need to repeat baseline endoscopies if > 45 days since date of baseline procedures

Exclusion Criteria:

  • Use of any other investigational agents ≤ 12 weeks prior to pre-registration
  • History of gastric or intestinal ulceration due to NSAID therapy
  • Uncontrolled intercurrent illness or recent surgical procedure that in the opinion of the investigative team would limit compliance with study requirements
  • History of invasive malignancy ≤ 3 years prior to pre-registration (exception: adequately treated carcinoma of the cervix, carcinoma in situ, or basal or squamous cell carcinomas of the skin)
  • History of any upper GI surgery that does not permit access to or evaluation of a 10 cm segment of the duodenum that includes the duodenal bulb, i.e. Whipple procedure or similar
  • Any histologically confirmed high grade dysplasia (HGD) or cancer, gastrointestinal bleeding and requirement for anticoagulation therapy after study start except for use of low dose aspirin
  • Exclusion of patients utilizing strong a moderate inhibitors of CYP2D6 and CYP3A4
  • Individuals with evidence of human immunodeficiency virus (HIV) infection will be excluded from the study even if the HIV viral load is undetectable on suppressive therapy. Many of the HIV suppression anti-viral medications are moderate/strong inhibitors of CYP2D6 and CYP3A4 and are exclusions based on above
  • Individuals with evidence of chronic hepatitis B virus (HBV) or C virus (HCV) infection will be excluded from the study, even if the HBV/HCV viral load is undetectable on suppressive therapy. Many of the HBV/HCV suppression anti-viral medications are moderate/strong inhibitors of CYP2D6 and CYP3A4 and are exclusions based on above
  • Individuals with active H. pylori infection that is untreated or refractory to standard antibiotic therapy
  • Patients with prior history of peptic ulcers complicated by bleeding, New York Heart Association (NYHA) Classification II-IV, active autoimmune diseases, on anticoagulants at risk of bleeding or abnormal corrected QT interval (QTc) prolongation will also be excluded. Patients enrolled in this trial are status post colectomy or subtotal colectomy (with either IPAA or IRA or ileo-colonic anastomosis) and thus would not be expected to be at significant risk of diverticulitis

Study Design

Enrollment

38 participants

Anticipated

Intervention Model

Single group

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

experimental: Prevention (TPST-1495)

Patients receive TPST-1495 PO QD for 6 months in the absence of unacceptable toxicity. Patients also undergo EGD and GI endoscopy with biopsy at baseline and end of treatment and undergo blood sample collection throughout the study.

Interventions

Biopsy Procedure

Undergo biopsy

Biospecimen Collection

Undergo blood sample collection

EP2/EP4 Antagonist TPST-1495

Given PO

Esophagogastroduodenoscopy

Undergo EGD

Gastrointestinal Endoscopy

Undergo GI endoscopy

Questionnaire Administration

Ancillary studies

Primary outcome measure

  • Percent change in duodenal polyp burden [ Time Frame: Baseline to 6 months ]
  • Incidence of adverse events [ Time Frame: Up to 7 months ]

Central Contacts and Locations

Locations

University of Wisconsin Carbone Cancer Center - University Hospital

Recruiting

Madison, Wisconsin, United States, 53792

Contacts

Lisa M. Barroilhet

608-265-2319barroilhet@wisc.edu

Principal Investigator:

Lisa M. Barroilhet

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 1, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-01.