TPST-1495 treatment for people with familial adenomatous polyposis
Phase 2 Study to Evaluate the Efficacy and Safety of TPST-1495 in Patients With Familial Adenomatous Polyposis (FAP)
This trial will try an oral drug called TPST-1495 to see if it reduces the number of polyps in the small bowel and colon in people with familial adenomatous polyposis.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 38 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | National Cancer Institute (NCI) NIH |
| Locations | 4 sites (Phoenix, Arizona and 3 other locations) |
| Trial ID | NCT06557733 on ClinicalTrials.gov |
What this trial studies
This is an open-label Phase II trial giving TPST-1495 orally once daily for six months to adults with familial adenomatous polyposis (FAP). The main goal is to see whether the drug reduces duodenal polyp burden, with safety monitored by recording adverse events. Patients undergo baseline and end-of-treatment esophagogastroduodenoscopy and gastrointestinal endoscopy with biopsies, and blood samples are collected during the study. Exploratory analyses include tissue immunohistochemistry for COX-2, beta-catenin, and Ki-67 and serum proteomics to correlate biomarkers with response.
Who should consider this trial
Good fit: Ideal candidates are adults with a confirmed genetic or clinical diagnosis of FAP who had prophylactic colectomy or sub-total colectomy at least 12 months earlier and who can stop NSAIDs as required before starting treatment.
Not a fit: Patients without FAP, those with recent postoperative complications or colectomy within the past 12 months, or those who cannot discontinue NSAIDs or have contraindications to the study drug are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, TPST-1495 could lower intestinal polyp burden and reduce future colorectal cancer risk, potentially delaying or reducing the need for additional surgery.
How similar studies have performed: Drugs that block prostaglandin signaling such as COX-2 inhibitors have previously reduced polyps in FAP, but dual EP2/EP4 antagonists like TPST-1495 represent a newer mechanism with limited clinical experience to date.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Phoenix, Arizona and 3 other locations
- Mayo Clinic Hospital in Arizona — Phoenix, Arizona, United States (Not_yet_recruiting)
- Mayo Clinic in Rochester — Rochester, Minnesota, United States (Not_yet_recruiting)
- Huntsman Cancer Institute/University of Utah — Salt Lake City, Utah, United States (Not_yet_recruiting)
- University of Wisconsin Carbone Cancer Center - University Hospital — Madison, Wisconsin, United States (Recruiting)
Study contacts
- Principal investigator: Niloy J Samadder — University of Wisconsin Carbone Cancer Center - University Hospital
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.