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Colorectal CarcinomaPhase 2NCT06557733

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

A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and EP2/EP4 Antagonist TPST-1495 in people with Colorectal Carcinoma and Familial Adenomatous Polyposis, run by National Cancer Institute (NCI) at 4 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy Procedure, Biospecimen Collection and EP2/EP4 Antagonist TPST-1495
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
4 sitesUnited States
Study dates
31 Mar 2026to 30 Jun 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States4 sites, 4 recruiting

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

    Lisa M. Barroilhet, 608-265-2319, barroilhet@wisc.edu

    Lisa M. Barroilhet

    Recruiting

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

    Niloy J. Samadder, 480-342-6263, Samadder.jewel@mayo.edu

    Niloy J. Samadder

    Recruiting

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

    Lisa A. Boardman, 507-284-2175, boardman.lisa@mayo.edu

    Lisa A. Boardman

    Not yet recruiting

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

    Jessica R. Stout, 801-585-6439, jessica.stout@utah.edu

    Jessica R. Stout

    Not yet recruiting

Other trials in United States

About this study

Official title: Phase 2 Study to Evaluate the Efficacy and Safety of TPST-1495 in Patients With Familial Adenomatous Polyposis (FAP)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

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

EXPLORATORY OBJECTIVES:

  1. 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.

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.

Being tested
Biopsy Procedure, Biospecimen Collection, EP2/EP4 Antagonist TPST-1495, Esophagogastroduodenoscopy, Gastrointestinal Endoscopy
Medical subject headings
Colorectal Neoplasms, Adenomatous Polyposis Coli

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • EP2/EP4 Antagonist TPST-1495Drug

    Also called Dual EP2/4 Antagonist TPST-1495, PGE2 EP2/EP4 Receptor Antagonist TPST-1495, Prostaglandin E2 Receptor EP2/EP4 Antagonist TPST-1495, TPST 1495

    Given PO

  • EsophagogastroduodenoscopyProcedure or surgery

    Also called EGD, Upper Endoscopy

    Undergo EGD

  • Gastrointestinal EndoscopyProcedure or surgery

    Undergo GI endoscopy

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT06557733
Study groupRoleWhat they receive
Prevention (TPST-1495)ExperimentalPatients 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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: EP2/EP4 Antagonist TPST-1495; Procedure: Esophagogastroduodenoscopy; Procedure: Gastrointestinal Endoscopy; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to 6 months

  2. 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.

    Measured: Up to 7 months

Secondary outcomes (1)

  1. 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.

    Measured: Baseline to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2024
  2. Study start31 Mar 2026
  3. Primary completion30 Jun 2027 (estimated)
  4. Study completion30 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06557733
Sponsor's protocol ID
NCI-2024-06758
Other IDs
NCI-2024-06758, UWI23-16-01, UWI23-16-01, P30CA014520, UG1CA242596, UG1CA242635
Status last verified
Aug 2026
First submitted
15 Aug 2024
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and EP2/EP4 Antagonist TPST-1495 in people with Colorectal Carcinoma and Familial Adenomatous Polyposis, run by National Cancer Institute (NCI) at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent change in duodenal polyp burden (time frame: Baseline to 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06557733.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.

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