A Phase IIa, Placebo-Controlled, Randomized Study of Daily Obeticholic Acid (OCA) to Reduce Intestinal Polyp Burden in Familial Adenomatous Polyposis (FAP)
This phase IIa trial investigates if giving obeticholic acid (OCA) is safe and has a beneficial effect on the number of polyps in the small bowel and colon in patients with familial adenomatous polyposis (FAP). FAP is a rare gene defect that increases the risk of developing cancer of the intestines and colon. OCA is a drug similar to a bile acid the body makes. It is fluid made and released by the liver. OCA binds to a receptor in the intestine that is believed to have a positive effect on preventing cancer development. OCA has been effective in treating primary biliary cholangitis (PBC), a liver disease, and is approved by the Food and Drug Administration (FDA) for use at a lower dose (10 mg). There have been studies showing that OCA decreases inflammation and fibrosis. However, it is not yet known whether OCA works on reducing the number of polyps in patients with FAP.
• Participants must have a diagnosis of phenotypic FAP with disease involvement of the duodenum and rectum as defined by:
‣ Genetic diagnosis: APC germline mutation (with or without family history) or obligate carrier
⁃ Clinical diagnosis: FAP phenotype with \> 100 adenomas in large intestine and participant has a family history of FAP
⁃ Clinical diagnosis: FAP phenotype who are status post colectomy for polyposis, participant has a family history of FAP, and 2 FAP experts agree to the diagnosis
⁃ Attenuated FAP diagnosis: APC germline mutation required
• Participants must have no evidence of active or recurrent invasive cancer for 6 months prior to screening and must be at least 6 months from any prior cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy or radiation)
• Age \>= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of OCA in participants \< 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Hemoglobin \>= 10 g/dL or hematocrit \>= 30%
• Leukocyte count \>= 3,500/microliter
• Platelet count \>= 100,000/microliter
• Absolute neutrophil count \>= 1,500/microliter
• Creatinine clearance (calculated if measured is not available) \>= 30 mL/min/1.73m\^2
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x the institutional upper limit of normal (ULN)
• Total bilirubin =\< 1.0 x ULN
• Alkaline phosphatase =\< 1.5 x ULN
• Gamma-glutamyl transferase (GGT) =\< 1.5 x ULN
• Presence of Spigelman stage II or III duodenal polyposis at screening
• Presence of intact rectum or ileo-rectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA) or end ileostomy
• Participants must have a negative test result for human immunodeficiency virus (HIV); if tested within the past 6 months, result will be accepted without repeating the test
• Participants must have negative test for hepatitis C virus (HCV) and B virus (HBV)
• Willing and able to adhere to the prohibitions and restrictions specified in the final approved protocol
• The effects of OCA 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, throughout the duration of study participation, and for at least 6 months after receiving the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Willingness to moderate alcohol intake (consuming no more than 1 or 2 alcoholic drinks per day for women and men, respectively)
• Ability to understand and the willingness to sign a written informed consent document