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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-06-07

Study Completion Date

2026-12-17

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVES:

I. To assess the activity of TPST-1495 in reducing duodenal polyp burden in patients with FAP.

II. To assess the safety of TPST-1495 in patients with FAP; we will evaluate the incidence of grade 2 or 3 adverse events.

SECONDARY OBJECTIVE:

I. The activity of TPST-1495 in reducing rectum/IPAA (ileal pouch-anal anastomosis) polyp burden in patients with FAP.

EXPLORATORY OBJECTIVES:

I. Reduction in intestinal polyp burden as a function of immunohistochemical staining at baseline and end of intervention (6-months) of rectal and duodenal tissue samples for COX-2 expression level, beta-catenin, and Ki-67.

II. Proteomic profile of serum correlated to clinical response to therapy compared between baseline and end of intervention.

III. Biospecimen acquisition. IV. TPST-1495 concentrations in plasma at pre-dose, 2-, and 4-hours post-dose at month 3 visit to assess steady-state pharmacokinetics.

OUTLINE:

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

After completion of study treatment, patients are followed up at 1 month.

Conditions

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Familial Adenomatous Polyposis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Biopsy Procedure

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

EP2/EP4 Antagonist TPST-1495

Intervention Type DRUG

Given PO

Esophagogastroduodenoscopy

Intervention Type PROCEDURE

Undergo EGD

Gastrointestinal Endoscopy

Intervention Type PROCEDURE

Undergo GI endoscopy

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Interventions

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Biopsy Procedure

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

EP2/EP4 Antagonist TPST-1495

Given PO

Intervention Type DRUG

Esophagogastroduodenoscopy

Undergo EGD

Intervention Type PROCEDURE

Gastrointestinal Endoscopy

Undergo GI endoscopy

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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Biopsy BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection 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 EGD Upper Endoscopy Enteroscopy

Eligibility Criteria

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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 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 with IRA (ileo-rectal 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
* Patients 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 including 90 days after discontinuing 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
* Patients 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
* Patients 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
* Patients 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 (with either IPAA or IRA) and thus would not be expected to be at risk of diverticulitis

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Niloy J Samadder

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin Carbone Cancer Center - University Hospital

Locations

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Mayo Clinic Hospital in Arizona

Phoenix, Arizona, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Site Status

University of Puerto Rico

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

Facility Contacts

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Niloy J. Samadder

Role: primary

Lisa A. Boardman

Role: primary

Jessica R. Stout

Role: primary

Lisa M. Barroilhet

Role: primary

Marcia R. Cruz-Correa

Role: primary