Trial Title:
An Investigational Drug (TPST-1495) in Patients With Familial Adenomatous Polyposis
NCT ID:
NCT06557733
Condition:
Familial Adenomatous Polyposis
Conditions: Official terms:
Colorectal Neoplasms
Nasopharyngeal Neoplasms
Adenomatous Polyposis Coli
Dinoprostone
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Prevention
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Prevention (TPST-1495)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Prevention (TPST-1495)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
EP2/EP4 Antagonist TPST-1495
Description:
Given PO
Arm group label:
Prevention (TPST-1495)
Other name:
Dual EP2/4 Antagonist TPST-1495
Other name:
PGE2 EP2/EP4 Receptor Antagonist TPST-1495
Other name:
Prostaglandin E2 Receptor EP2/EP4 Antagonist TPST-1495
Other name:
TPST 1495
Other name:
TPST-1495
Other name:
TPST1495
Intervention type:
Procedure
Intervention name:
Esophagogastroduodenoscopy
Description:
Undergo EGD
Arm group label:
Prevention (TPST-1495)
Other name:
EGD
Other name:
Upper Endoscopy
Intervention type:
Procedure
Intervention name:
Gastrointestinal Endoscopy
Description:
Undergo GI endoscopy
Arm group label:
Prevention (TPST-1495)
Other name:
Enteroscopy
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Prevention (TPST-1495)
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.
Detailed description:
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 examine the number of
patients with 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.
Criteria for eligibility:
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 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic Hospital in Arizona
Address:
City:
Phoenix
Zip:
85054
Country:
United States
Contact:
Last name:
Niloy J. Samadder
Phone:
480-342-6263
Email:
Samadder.jewel@mayo.edu
Investigator:
Last name:
Niloy J. Samadder
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Contact:
Last name:
Lisa A. Boardman
Phone:
507-284-2175
Email:
boardman.lisa@mayo.edu
Investigator:
Last name:
Lisa A. Boardman
Email:
Principal Investigator
Facility:
Name:
Huntsman Cancer Institute/University of Utah
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Contact:
Last name:
Jessica R. Stout
Phone:
801-585-6439
Email:
jessica.stout@utah.edu
Investigator:
Last name:
Jessica R. Stout
Email:
Principal Investigator
Facility:
Name:
University of Wisconsin Carbone Cancer Center - University Hospital
Address:
City:
Madison
Zip:
53792
Country:
United States
Contact:
Last name:
Lisa M. Barroilhet
Phone:
608-265-2319
Email:
barroilhet@wisc.edu
Investigator:
Last name:
Lisa M. Barroilhet
Email:
Principal Investigator
Facility:
Name:
University of Puerto Rico
Address:
City:
San Juan
Zip:
00936
Country:
Puerto Rico
Contact:
Last name:
Marcia R. Cruz-Correa
Phone:
787-772-8300
Phone ext:
1216
Email:
marcia.cruzcorrea@upr.edu
Investigator:
Last name:
Marcia R. Cruz-Correa
Email:
Principal Investigator
Start date:
February 4, 2025
Completion date:
December 17, 2026
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06557733
