RECRUITING

Testing for Safety and Colorectal Cancer Preventive Effects of ONC201

Conditions

Colorectal Adenomatous Polyp Colorectal Carcinoma Familial Adenomatous Polyposis Multiple Adenomatous Polyps

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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

The purpose of this phase I trial is to test the safety and cancer preventive effects of different doses of ONC201 in people with familial adenomatous polyposis (FAP) or a history of multiple polyps. People with familial adenomatous polyposis (FAP) or a history of multiple polyps are at higher than average risk of developing colorectal cancer. ONC201, now known as dordaviprone, is a drug that may stop cancer cells from growing. This drug has been shown in previous studies to cause cancer cell death but not harm normal cells. If successful, this study may help us develop a new option for colorectal cancer prevention.

Official Title

Phase 1 Trial of ONC201 for Chemoprevention in Colorectal Cancer

Quick Facts

Study Start:2025-10-06

Study Completion:2028-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05630794

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
* Be identified as high risk for recurrent colorectal adenomas, as defined by: * A diagnosis of FAP AND/OR * Findings of either \> 5 small (less than 1 cm) adenomas OR \>= 3 with at least one \>= 10 mm on most recent colonoscopy performed in the past 5 years * Be \>= 18 years of age on day of signing informed consent * Have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%) * Leukocytes \>= 3,000/microliter * Absolute neutrophil count \>= 1,000/microliter * Platelets \>= 100,000/microliter * Total bilirubin within normal institutional limits * Aspartate aminotransferase (AST) (serum (glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (\[SGPT\]) =\< 1.5 x institutional upper limit of normal * Creatinine =\< 1.5 x institutional upper limit of normal * Participant is due to undergo a standard of care lower gastrointestinal (GI) colonoscopy for detection and removal of colorectal polyps. On this colonoscopy, participant is required to have: * Two (2) adenomatous polyps of at least five (5) mm in size * At least one (1) polyp within reach of a flexible sigmoidoscope (which will be retained in the colon or rectum and marked) * In addition to polypectomy, six (6) biopsies of normal colonic mucosa \>= 1 cm from a collected polyp will also be collected * Willing to undergo a second, research intent endoscopic procedure (either sigmoidoscopy or colonoscopy), approximately 12 weeks after initiating ONC201 treatment * Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures * Life expectancy of at least 5-years * ONC201 is an imipridone agent with the potential for teratogenic or abortifacient effects. For this reason and because imipridones potential teratogenic effects are unknown, men and women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for four weeks after study treatment is completed. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should STOP the study medication and inform her study physician immediately * Ability to understand and the willingness to sign a written informed consent document	* Prior history of hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome * Participants may not be currently receiving any other investigational agents or have received any investigational agents within the past four weeks * Prior history of invasive colorectal cancer * Prior invasive active neoplasm that is progressing or requires active treatment within 3 years from registration. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Participants with a history of prior invasive neoplasm diagnosed and treated greater than 3 years form registration may be considered with consultation of the primary investigator * Prior history of exposure to cytotoxic chemotherapy or ONC201 * History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 * 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 * Pregnant and women who are nursing are excluded from this study because ONC201 is an imipridone agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with ONC201, breastfeeding should be discontinued if the mother is treated with ONC201 * Concomitant use of strong CYP3A4/5 inducers/inhibitors. These agents must be discontinued at least 72-hours prior to beginning ONC201

Inclusion Criteria

Exclusion Criteria

* Be identified as high risk for recurrent colorectal adenomas, as defined by:
* A diagnosis of FAP AND/OR
* Findings of either \> 5 small (less than 1 cm) adenomas OR \>= 3 with at least one \>= 10 mm on most recent colonoscopy performed in the past 5 years
* Be \>= 18 years of age on day of signing informed consent
* Have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
* Leukocytes \>= 3,000/microliter
* Absolute neutrophil count \>= 1,000/microliter
* Platelets \>= 100,000/microliter
* Total bilirubin within normal institutional limits
* Aspartate aminotransferase (AST) (serum (glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (\[SGPT\]) =\< 1.5 x institutional upper limit of normal
* Creatinine =\< 1.5 x institutional upper limit of normal
* Participant is due to undergo a standard of care lower gastrointestinal (GI) colonoscopy for detection and removal of colorectal polyps. On this colonoscopy, participant is required to have:
* Two (2) adenomatous polyps of at least five (5) mm in size
* At least one (1) polyp within reach of a flexible sigmoidoscope (which will be retained in the colon or rectum and marked)
* In addition to polypectomy, six (6) biopsies of normal colonic mucosa \>= 1 cm from a collected polyp will also be collected
* Willing to undergo a second, research intent endoscopic procedure (either sigmoidoscopy or colonoscopy), approximately 12 weeks after initiating ONC201 treatment
* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
* Life expectancy of at least 5-years
* ONC201 is an imipridone agent with the potential for teratogenic or abortifacient effects. For this reason and because imipridones potential teratogenic effects are unknown, men and women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for four weeks after study treatment is completed. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should STOP the study medication and inform her study physician immediately
* Ability to understand and the willingness to sign a written informed consent document

* Prior history of hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome
* Participants may not be currently receiving any other investigational agents or have received any investigational agents within the past four weeks
* Prior history of invasive colorectal cancer
* Prior invasive active neoplasm that is progressing or requires active treatment within 3 years from registration. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Participants with a history of prior invasive neoplasm diagnosed and treated greater than 3 years form registration may be considered with consultation of the primary investigator
* Prior history of exposure to cytotoxic chemotherapy or ONC201
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201
* 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
* Pregnant and women who are nursing are excluded from this study because ONC201 is an imipridone agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with ONC201, breastfeeding should be discontinued if the mother is treated with ONC201
* Concomitant use of strong CYP3A4/5 inducers/inhibitors. These agents must be discontinued at least 72-hours prior to beginning ONC201

Contacts and Locations

Principal Investigator

Alexander G Raufi, MD

PRINCIPAL_INVESTIGATOR

Brown University and Rhode Island Hospital

Study Locations (Sites)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109

United States

Washington University School of Medicine

St Louis, Missouri, 63110

United States

Cleveland Clinic Foundation

Cleveland, Ohio, 44195

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

United States

Rhode Island Hospital

Providence, Rhode Island, 02903

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Alexander G Raufi, MD, PRINCIPAL_INVESTIGATOR, Brown University and Rhode Island Hospital

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 Date2025-10-06

Study Completion Date2028-03-01

Study Record Updates

Study Start Date2025-10-06

Study Completion Date2028-03-01

Terms related to this study

Additional Relevant MeSH Terms

Colorectal Adenomatous Polyp
Colorectal Carcinoma
Familial Adenomatous Polyposis
Multiple Adenomatous Polyps