Testing for Safety and Colorectal Cancer Preventive Effects of ONC201
NCT ID: NCT05630794
Last Updated: 2026-02-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
36 participants
INTERVENTIONAL
2025-10-06
2028-03-01
Brief Summary
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Detailed Description
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I. To evaluate the safety and toxicity of Akt/ERK Inhibitor ONC201 (ONC201) for the indication of cancer prevention in a healthy population of individuals who are at high risk (FAP and/or history of multiple adenomas \[excluding hereditary nonpolyposis colorectal cancer (HNPCC)\]) for recurrent colorectal adenomas.
SECONDARY OBJECTIVES:
I. To determine the dose(s) of ONC201 that yield(s) a statistically significant increase in human adenoma tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression.
II. To determine the dose(s) of ONC201 that yield(s) a statistically significant increase in normal human mucosa TRAIL expression.
EXPLORATORY OBJECTIVES:
I. To evaluate the impact of ONC201 on:
Ia. Cytokine/immune response profiles (with attention to interleukin \[IL\]-10, IL-17A, tumor necrosis factor \[TNF\]-alpha, IL-6, granzyme A, and perforin) in sera, normal colonic mucosa, and adenomas; Ib. Serum TRAIL concentration; Ic. Serum prolactin concentration; Id. Proliferation markers (Ki67), cell death markers (BCL2, Caspase 3), stemness markers (LGR5, CD44, CD133, ALDH), and natural killer (NK) cell infiltration in adenomas and in normal colonic mucosa; Ie. To evaluate for associations between observed toxicity and TRAIL expression; If. To establish organoids ex vivo and compare adenoma-derived organoid take rates between samples obtained prior to and following treatment.
OUTLINE: This is a dose-escalation study.
Patients receive ONC201 orally (PO) once weekly (QW) or once every 3 weeks (Q3W) for 13 weeks. Patients also undergo collection of blood, tissue biopsy, and sigmoidoscopy/colonoscopy throughout the study.
After completion of study treatment, patients are followed up at 21-35 days.
Conditions
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Study Design
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NA
SINGLE_GROUP
PREVENTION
NONE
Study Groups
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Prevention (ONC201, biopsy, sigmoidoscopy, colonoscopy)
Patients receive ONC201 PO QW or Q3W for 13 weeks. Patients also undergo collection of blood, tissue biopsy, and sigmoidoscopy/colonoscopy throughout the study.
Biopsy Procedure
Undergo biopsy
Biospecimen Collection
Undergo collection of blood
Colonoscopy
Undergo colonoscopy
Dordaviprone
Given PO
Questionnaire Administration
Ancillary studies
Sigmoidoscopy
Undergo sigmoidoscopy
Interventions
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Biopsy Procedure
Undergo biopsy
Biospecimen Collection
Undergo collection of blood
Colonoscopy
Undergo colonoscopy
Dordaviprone
Given PO
Questionnaire Administration
Ancillary studies
Sigmoidoscopy
Undergo sigmoidoscopy
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
Exclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Alexander G Raufi, MD
Role: PRINCIPAL_INVESTIGATOR
Brown University and Rhode Island Hospital
Locations
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University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, United States
Washington University School of Medicine
St Louis, Missouri, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Rhode Island Hospital
Providence, Rhode Island, United States
Countries
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Facility Contacts
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Other Identifiers
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NCI-2022-09737
Identifier Type: REGISTRY
Identifier Source: secondary_id
UMCC 2022.038
Identifier Type: OTHER
Identifier Source: secondary_id
UMI22-09-02
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2022-09737
Identifier Type: -
Identifier Source: org_study_id
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