An Investigational Drug (TPST-1495) in Patients With Familial Adenomatous Polyposis

NCT06557733 | Recruiting Phase 2 DMC FDA Drug

• 5 other identifiers: NCI-2024-06758UWI23-16-01P30CA014520UG1CA242596UG1CA242635
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 4

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

Familial Adenomatous Polyposis; Colorectal Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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 6.0. Will be summarized as a proportion with a 1-sided 90% confidence interval.

  Up to 7 months

Secondary Outcomes (1)

• Percent change in rectal/pouch polyp burden

  Baseline to 6 months

Other Outcomes (2)

• Percent change in immunohistochemical staining levels

  Baseline to 6 months

• Proteomic profile

  Baseline to 6 months

Study Arms (1)

Prevention (TPST-1495)

EXPERIMENTAL

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: EP2/EP4 Antagonist TPST-1495; Procedure: Esophagogastroduodenoscopy; Procedure: Gastrointestinal Endoscopy; Other: Questionnaire Administration

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Prevention (TPST-1495)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Prevention (TPST-1495)

EP2/EP4 Antagonist TPST-1495 DRUG

Given PO

Also known as: Dual EP2/4 Antagonist TPST-1495, PGE2 EP2/EP4 Receptor Antagonist TPST-1495, Prostaglandin E2 Receptor EP2/EP4 Antagonist TPST-1495, TPST 1495, TPST-1495, TPST1495

Prevention (TPST-1495)

Esophagogastroduodenoscopy PROCEDURE

Undergo EGD

Also known as: EGD, Upper Endoscopy

Prevention (TPST-1495)

Gastrointestinal Endoscopy PROCEDURE

Undergo GI endoscopy

Also known as: Enteroscopy

Prevention (TPST-1495)

Questionnaire Administration OTHER

Ancillary studies

Prevention (TPST-1495)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

NOT YET RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

NOT YET RECRUITING

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

NOT YET RECRUITING

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Adenomatous Polyposis Coli

Interventions

Biopsy; Specimen Handling; Endoscopy, Digestive System; Gastroscopy; Endoscopy, Gastrointestinal

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Syndromes, Hereditary; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Diagnostic Techniques, Digestive System; Endoscopy; Digestive System Surgical Procedures; Minimally Invasive Surgical Procedures

Study Officials

• Niloy J Samadder

  University of Wisconsin Carbone Cancer Center - University Hospital

  PRINCIPAL INVESTIGATOR

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: August 15, 2024
• First Posted: August 16, 2024
• Study Start: March 31, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (4)