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Colorectal Adenomatous PolypPhase 1NCT05630794

Testing for Safety and Colorectal Cancer Preventive Effects of ONC201

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Colonoscopy in people with Colorectal Adenomatous Polyp and Colorectal Carcinoma, run by National Cancer Institute (NCI) at 5 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy Procedure, Biospecimen Collection and Colonoscopy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
5 sitesUnited States
Study dates
6 Oct 2025to 1 May 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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 (in participants who have undergone prior colectomy and for whom colonoscopy is not feasible, an appropriate standard-of-care lower endoscopic evaluation may be substituted for the baseline colonoscopy at the site investigator's discretion) 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

Who cannot join

  • 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
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  • 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/moderate CYP3A4/5 inducers/inhibitors. These agents must be discontinued at least 72-hours prior to beginning ONC201
  • Any of the following cardiac criteria:
  • Prolongation of corrected QT (QTc) interval (QTc interval > 480 milliseconds, preferably using Frederica's QT correction formula), confirmed on electrocardiogram (ECG) tracings performed during screening
  • A history of Torsades de pointes, heart failure, or family history of prolonged QT Syndrome
  • Concomitant use of drugs that are known to prolong QT and have a known risk of torsade de pointes (TdP) unless they are willing to stop these medications and possibly change to an alternative non-excluded medication to treat the same condition at least 72 hours prior to beginning ONC201

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

5 sites in 1 country

United States5 sites, 5 recruiting

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

    Elena M. Stoffel, 734-936-0781, estoffel@med.umich.edu

    Elena M. Stoffel

    Recruiting

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

    Carol A. Burke, 216-444-6864, BURKEC1@ccf.org

    Carol A. Burke

    Recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Peter P. Stanich, 614-293-6255, peter.stanich@osumc.edu

    Peter P. Stanich

    Recruiting

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

    Alexander G. Raufi, 401-787-0988, alexander_raufi@brown.edu

    Alexander G. Raufi

    Not yet recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Paul E. Wise, 314-454-7177, wisepe@wustl.edu

    Paul E. Wise

    Not yet recruiting

Other trials in United States

About this study

Official title: Phase I Trial of ONC201 for Chemoprevention of Colorectal Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the safety and toxicity of dordaviprone (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:

  1. 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:

  1. 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. Additionally, patients undergo colonoscopy or lower endoscopic evaluation during screening.

After completion of study treatment, patients are followed up at 21-35 days.

Being tested
Biopsy Procedure, Biospecimen Collection, Colonoscopy, Dordaviprone Hydrochloride, Endoscopic Procedure
Medical subject headings
Colorectal Neoplasms, Adenomatous Polyposis Coli

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • ColonoscopyProcedure or surgery

    Undergo colonoscopy

  • Dordaviprone HydrochlorideDrug

    Also called Modeyso

    Given PO

  • Endoscopic ProcedureProcedure or surgery

    Also called Endoscopic Examination, Endoscopy, ES

    Undergo lower endoscopic evaluation

  • Questionnaire AdministrationOther

    Ancillary studies

  • SigmoidoscopyProcedure or surgery

    Also called Proctosigmoidoscopy

    Undergo sigmoidoscopy

Study groups in NCT05630794
Study groupRoleWhat they receive
Prevention (ONC201, biopsy, sigmoidoscopy, colonoscopy)ExperimentalPatients receive ONC201 PO QW or Q3W for 13 weeks. Patients also undergo collection of blood, tissue biopsy, and sigmoidoscopy/colonoscopy throughout the study. Additionally, patients undergo colonoscopy or lower endoscopic evaluation during screening.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Colonoscopy; Drug: Dordaviprone Hydrochloride; Procedure: Endoscopic Procedure; Other: Questionnaire Administration; Procedure: Sigmoidoscopy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of participants with unacceptable toxicity

    Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 35 days post last dose of ONC201

Secondary outcomes (2)

  1. Mean change in human adenoma tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression in polyps induced by ONC201

    The TRAIL expression in polyps obtained during pre-treatment colonoscopy and again during sigmoidoscopy after 12 weeks of treatment will be measured. The mean difference in this change is compared between time points by means of a paired t-test. For skewed outcomes, the nonparametric Wilcoxon signed-rank test will be employed.

    Measured: Baseline up to week 13 end of treatment

  2. Mean change in normal human mucosa TRAIL expression induced by ONC201

    The TRAIL expression in polyps obtained during pre-treatment colonoscopy and again during sigmoidoscopy after 12 weeks of treatment will be measured. The mean difference in this change is compared between time points by means of a paired t-test. For skewed outcomes, the nonparametric Wilcoxon signed-rank test will be employed.

    Measured: Baseline up to week 13 end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2022
  2. Study start6 Oct 2025
  3. Primary completion1 Jul 2028 (estimated)
  4. Study completion1 May 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05630794
Sponsor's protocol ID
NCI-2022-09737
Other IDs
NCI-2022-09737, UMCC 2022.038, UMI22-09-02, P30CA046592, UG1CA242632
Status last verified
Oct 2026
First submitted
29 Nov 2022
Last updated
15 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Colonoscopy in people with Colorectal Adenomatous Polyp and Colorectal Carcinoma, run by National Cancer Institute (NCI) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of participants with unacceptable toxicity (time frame: Up to 35 days post last dose of ONC201). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05630794.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.

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