Testing a drug called obeticholic acid for patients with familial adenomatous polyposis

A Phase IIa, Placebo-Controlled, Randomized Study of Daily Obeticholic Acid (OCA) to Reduce Intestinal Polyp Burden in Familial Adenomatous Polyposis (FAP)

This study is testing a drug called obeticholic acid to see if it can help reduce the size of polyps in people with familial adenomatous polyposis, a genetic condition that raises their risk of intestinal cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: National Cancer Institute (NCI) (NIH)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 7 sites (Scottsdale, Arizona and 6 other locations)
• Trial ID: NCT05223036 on ClinicalTrials.gov

What this trial studies

This phase IIa trial evaluates the safety and effectiveness of obeticholic acid (OCA) in reducing polyp burden in patients with familial adenomatous polyposis (FAP), a genetic condition that increases cancer risk in the intestines. Participants will receive either OCA or a placebo, and the primary objective is to measure the effect on duodenal polyp size. Secondary objectives include assessing safety, evaluating polyp burden in the rectum, and analyzing gene expression changes. The study aims to provide insights into the potential of OCA as a treatment for FAP-related polyps.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a confirmed diagnosis of familial adenomatous polyposis and specific disease involvement in the duodenum and rectum.

Not a fit: Patients with active or recurrent invasive cancer or those under 18 years of age may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of cancer in patients with familial adenomatous polyposis by decreasing polyp formation.

How similar studies have performed: While obeticholic acid has shown effectiveness in treating other conditions, this specific application for familial adenomatous polyposis is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* Prior use of study drug
* Duodenal or rectal/pouch polyp burden that is not quantifiable
* Histologically-confirmed high-grade dysplasia or cancer on biopsy at screening
* Individuals with active, known or suspected chronic liver disease including cirrhosis, nonalcoholic steatohepatitis (NASH) with liver fibrosis, NASH with cirrhosis, primary sclerosing cholangitis, biliary atresia
* Individuals with acute cholecystitis (defined by a syndrome of right upper quadrant pain, fever, and leukocytosis associated with gallbladder inflammation)
* Individuals with a history of pancreatitis or presence of pancreatic abnormalities suggestive of increased risk of pancreatitis
* Individuals with hepatic steatosis and velocity \> 1.7 meters/second (m/s) as determined by liver ultrasound elastography
* Individuals with hyperlipidemia not well controlled with the use of pharmacotherapy and/or dietary modifications
* History of severe, progressive, or uncontrolled renal, genitourinary, hepatic, hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic disturbances, or signs and symptoms thereof
* Pregnant, breast-feeding, or women of childbearing potential unwilling to use a reliable contraceptive method. Pregnant women are excluded from this study because OCA is an agent with unknown effects on the developing human fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OCA, breastfeeding should be discontinued if the mother is treated with OCA
* Known hypersensitivity, allergies, or intolerance to the study drug or compounds of similar chemical or biologic composition
* Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures
* Participants may not be receiving any other investigational agents
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Individuals with active and untreated hepatitis C virus (HCV) and/or or hepatitis B virus (HBV) infection
* Individuals with HIV infection are eligible for participation if:

  * CD4+ count \>= 300/uL
  * Viral load is undetectable
  * Receiving highly active antiretroviral therapy (HAART) without known or suspected drug interactions with OCA
  * Consultation with the participant's infectious disease specialist may be obtained
* Individuals taking the drugs listed below may not be randomized unless they are willing to stop the medications (and possibly change to alternative non-excluded medications to treat the same conditions) no less than 5 half-lives days prior to starting OCA or placebo on this study. Consultation with the participant's primary care provider may be obtained but is not required. The use of the following drugs or drug classes is prohibited during OCA/placebo treatment:

  * Investigational agents
  * Bile acid sequestrants (bile acid binding resins): cholestyramine, colestipol, or colesevelam
  * Bile salt efflux pump (BSEP) inhibitors
  * Clozapine
  * Theophylline derivatives
  * Tizanidine
  * Warfarin
  * Hepatotoxic drugs such as amiodarone, sodium valproate, certain herbal/dietary supplements, and long-term doxycycline or tetracycline

Where this trial is running

Scottsdale, Arizona and 6 other locations

• Mayo Clinic in Arizona — Scottsdale, Arizona, United States (Not_yet_recruiting)
• University of Kansas Cancer Center — Kansas City, Kansas, United States (Recruiting)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• University of Michigan Comprehensive Cancer Center — Ann Arbor, Michigan, United States (Recruiting)
• Cleveland Clinic Foundation — Cleveland, Ohio, United States (Recruiting)
• M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• University of Puerto Rico — San Juan, Puerto Rico (Recruiting)

Study contacts

• Principal investigator: Eduardo Vilar-Sanchez — M.D. Anderson Cancer Center

Conditions Attenuated Familial Adenomatous Polyposis; Colorectal Carcinoma; Duodenal Carcinoma; Familial Adenomatous Polyposis