NCT05630794

Testing for Safety and Colorectal Cancer Preventive Effects of ONC201

Phase I Trial of ONC201 for Chemoprevention of Colorectal Cancer

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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. 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.

Detailed description

PRIMARY OBJECTIVE: I. 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: 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

• Colorectal Adenomatous Polyp
• Colorectal Carcinoma
• Familial Adenomatous Polyposis
• Multiple Adenomatous Polyps

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo collection of blood
PROCEDURE	Colonoscopy	Undergo colonoscopy
DRUG	Dordaviprone Hydrochloride	Given PO
OTHER	Questionnaire Administration	Ancillary studies
PROCEDURE	Sigmoidoscopy	Undergo sigmoidoscopy

Timeline

• Start date: 2025-10-06
• Primary completion: 2027-05-01
• Completion: 2028-03-01
• First posted: 2022-11-30
• Last updated: 2026-04-13

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study