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

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