TPST-1495 for Adenomatous Polyposis

Not yet recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: NSAIDs, CYP2D6 inhibitors

Disqualifiers: HIV, Hepatitis B/C, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how effectively a new drug, TPST-1495, can reduce the number of polyps (small growths) in the small bowel and colon for individuals with familial adenomatous polyposis (FAP), a condition that increases colon cancer risk. TPST-1495 blocks specific receptors involved in polyp formation. Individuals with FAP, particularly those who have undergone surgery to remove part of their colon and are willing to stop certain anti-inflammatory drugs, might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

You will need to stop taking non-steroidal anti-inflammatory drugs (NSAIDs) 5 days before starting the study treatment and limit their use during the study. The protocol does not specify other medication restrictions, but certain antiviral medications and drugs affecting liver enzymes may be excluded.

Is there any evidence suggesting that TPST-1495 is likely to be safe for humans?

Research has shown that TPST-1495 has been tested in patients with various solid tumors. These studies found that doctors could generally manage the treatment's mild side effects.

The studies also indicated that TPST-1495 performed as intended without causing major harm. Since this trial is in Phase 2, TPST-1495 has already passed initial safety tests in earlier phases, suggesting it is generally well-tolerated.

Overall, while no treatment is completely risk-free, TPST-1495 has demonstrated a safety profile considered acceptable for further clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for adenomatous polyposis, which often involves surgery or endoscopic removal of polyps, TPST-1495 is an oral medication that patients can take daily. Researchers are excited about TPST-1495 because it has a unique mechanism of action, targeting specific pathways involved in the growth of polyps, which could potentially prevent their formation altogether. This non-invasive approach could offer a more convenient and less risky alternative to current treatments, making it an innovative option in managing the condition.

What evidence suggests that TPST-1495 might be an effective treatment for familial adenomatous polyposis?

Research shows that TPST-1495, the treatment under study in this trial, might help reduce the number of polyps in people with familial adenomatous polyposis (FAP). This treatment blocks certain receptors involved in polyp growth. Specifically, TPST-1495 targets the EP2 and EP4 receptors, linked to polyp formation, while sparing other receptors that support the immune system. Previous studies on similar drugs have shown that blocking these receptors can reduce polyp growth, suggesting that TPST-1495 could be effective. Although more research is needed, the design of this drug indicates it might be a useful way to manage polyp growth in FAP. ^{1 2 4 6 7}

Who Is on the Research Team?

Niloy J Samadder

Principal Investigator

University of Wisconsin Carbone Cancer Center - University Hospital

Are You a Good Fit for This Trial?

This trial is for patients with familial adenomatous polyposis (FAP), a condition causing many polyps in the colon and increasing colon cancer risk. Details on who can join or reasons for exclusion are not provided.

Inclusion Criteria

Ability to understand and sign a written informed consent document

H. pylori negative confirmed with gastric biopsy at screening EGD

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

Use of any other investigational agents ≤ 12 weeks prior to pre-registration

I have had cancer within the last 3 years, with some exceptions.

Evidence of human immunodeficiency virus (HIV) infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TPST-1495 orally once daily for 6 months. They also undergo esophagogastroduodenoscopy (EGD) and gastrointestinal (GI) endoscopy with biopsy at baseline and end of treatment, and blood sample collection throughout the study.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

1 month

What Are the Treatments Tested in This Trial?

Interventions

• TPST-1495

Trial Overview The trial tests TPST-1495, which targets specific receptors to potentially reduce polyp numbers in the small bowel and colon of FAP patients. It involves endoscopies, tissue collection, biopsies, and questionnaires.

How Is the Trial Designed?

Group I: Prevention (TPST-1495) Experimental Treatment 6 Interventions

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. reporter.nih.gov reporter.nih.gov/project-details/10927554

75N91019D00020-0-759102300001-1 The purpose of this Task Order is to evaluate the efficacy and preliminary safety of TPST-1495 for the prevention of Colorectal Cancer (CRC) associated with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06557733?cond=Familial%20adenomatous%20polyposis%202%20OR%20%22adenomas,%20multiple%20colorectal,%20autosomal%20recessive%22%20OR%20%22%20colorectal%20adenomatous%20polyposis,%20autosomal%20recessive%22%20OR%20%22%20familial%20adenomatous%20polyposis,%202%22%20OR%20%22%20familial%20adenomatous%20polyposis,%20type%202%22%20OR%20%22%20FAP2%22%20OR%20%22%20MAP%22%20OR%20%22%20MUTYH-associated%20polyposis%22%20OR%20%22%20MUTYH-related%20AFAP%22%20OR%20%22%20MUTYH-related%20attenuated%20familial%20adenomatous%20polyposis%22%20OR%20%22%20MUTYH-related%20attenuated%20familial%20polyposis%20coli%22%20OR%20%22%20MUTYH-related%20attenuated%20FAP%22&aggFilters=status:not%20rec&viewType=Table&rank=2

An Investigational Drug (TPST-1495) in Patients With ... 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 ...

3. ir.tempesttx.com ir.tempesttx.com/news-releases/news-release-details/fda-study-may-proceed-notice-received-phase-2-trial-tpst-1495

FDA Study May Proceed Notice Received for Phase 2 Trial ... The primary efficacy objective is to assess the activity of TPST-1495 in reducing duodenal polyp burden in patients with FAP comparing baseline ...

4. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/promising-fap-treatment-phase-2-trial-of-tpst-1495-approved-by-fda/

Promising FAP Treatment: Phase 2 Trial of TPST-1495 ... The initiation of this Phase 2 trial addresses this unmet need by exploring the potential of TPST-1495 to reduce duodenal polyp burden and ...

5. gastroenterologyadvisor.com gastroenterologyadvisor.com/news/dual-ep2-ep4-antagonist-designated-orphan-drug-for-familial-adenomatous-polyposis/

Dual EP2/EP4 Antagonist Designated Orphan Drug for ... The primary efficacy endpoint is the percent change from baseline in duodenal polyp burden at 6 months. Data from the study are expected in 2026 ...

6. ctv.veeva.com ctv.veeva.com/study/an-investigational-drug-tpst-1495-in-patients-with-familial-adenomatous-polyposis

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

7. sigma.larvol.com sigma.larvol.com/product.php?e1=821513&tab=newstrac

TPST-1495 News In patients with heavily treated solid tumors, primarily MSS CRC, TPST-1495 had pharmacodynamic activity, a manageable safety profile, and a potential signal of ...