SUSPENDED

Testing Obeticholic Acid for Familial Adenomatous Polyposis

Conditions

Attenuated Familial Adenomatous Polyposis Colorectal Carcinoma Duodenal Carcinoma Familial Adenomatous Polyposis

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-01-19

Study Completion:2026-02-21

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:SUSPENDED

Study ID

NCT05223036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Principal Investigator

Eduardo Vilar-Sanchez

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259

United States

University of Kansas Cancer Center

Kansas City, Kansas, 66160

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109

United States

Cleveland Clinic Foundation

Cleveland, Ohio, 44195

United States

M D Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Eduardo Vilar-Sanchez, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-01-19

Study Completion Date2026-02-21

Study Record Updates

Study Start Date2023-01-19

Study Completion Date2026-02-21

Terms related to this study

Additional Relevant MeSH Terms

Attenuated Familial Adenomatous Polyposis
Colorectal Carcinoma
Duodenal Carcinoma
Familial Adenomatous Polyposis