Testing Obeticholic Acid for Familial Adenomatous Polyposis

NCT05223036 | Suspended Phase 2 DMC FDA Drug

• 5 other identifiers: NCI-2022-003412021-0286MDA20-01-01P30CA016672UG1CA242609
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 7

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Percentage change in duodenal polyp burden

  Change from baseline will be summarized by treatment arm. The difference in change from baseline between active treatment arms and the placebo arm will also be summarized.

  Baseline to 6 months

Secondary Outcomes (8)

• Incidence of adverse events

  Up to 21 days after completion of treatment

• Absolute differences in the levels of serum FGF19 and C4

  Baseline to 6 months

• Percentage change in the number of duodenal polyps

  Baseline to 6 months

• Percentage change in the number of colorectal, rectal/pouch polyps

  Baseline to 6 months

• Percentage change in colorectal, rectal/pouch polyp burden

  Baseline to 6 months

Study Arms (2)

Arm I (OCA)

EXPERIMENTAL

Patients receive OCA PO QD for 6 months in the absence of unacceptable toxicity. Patients also undergo GI endoscopy with biopsy and collection of blood samples at screening and on study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Gastrointestinal Endoscopy; Biological: Obeticholic Acid; Other: Questionnaire Administration

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo PO QD for 6 months in the absence of unacceptable toxicity. Patients also undergo GI endoscopy with biopsy and collection of blood samples at screening and on study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Gastrointestinal Endoscopy; Drug: Placebo Administration; Other: Questionnaire Administration

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Arm I (OCA); Arm II (placebo)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (OCA); Arm II (placebo)

Gastrointestinal Endoscopy PROCEDURE

Undergo GI endoscopy

Also known as: Enteroscopy

Arm I (OCA); Arm II (placebo)

Obeticholic Acid BIOLOGICAL

Given PO

Also known as: INT-747, Ocaliva

Arm I (OCA)

Questionnaire Administration OTHER

Ancillary studies

Arm I (OCA); Arm II (placebo)

Placebo Administration DRUG

Given PO

Arm II (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Puerto Rico

San Juan, 00936, Puerto Rico

Location

MeSH Terms

Conditions

Attenuated familial adenomatous polyposis; Colorectal Neoplasms; Duodenal Neoplasms; Adenomatous Polyposis Coli

Interventions

Biopsy; Specimen Handling; Endoscopy, Gastrointestinal; obeticholic acid

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Duodenal Diseases; Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Syndromes, Hereditary; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Endoscopy; Digestive System Surgical Procedures; Minimally Invasive Surgical Procedures

Study Officials

• Eduardo Vilar-Sanchez

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: February 3, 2022
• Study Start: January 19, 2023
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): February 21, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

PR (1); US (6)