Ignite Creation Date:
2025-12-25 @ 1:34 AM
Ignite Modification Date:
2025-12-27 @ 11:13 PM
Study NCT ID:
NCT05630794
Status:
RECRUITING
Last Update Posted:
2025-08-15
First Post:
2022-11-29
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Testing for Safety and Colorectal Cancer Preventive Effects of ONC201
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase 1 Trial of ONC201 for Chemoprevention in Colorectal Cancer
Status:
RECRUITING
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial tests the safety, side effects, and best dose of ONC201 in preventing colorectal cancer in patients with familial adenomatous polyposis (FAP) or a history of multiple polyps. ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description:
PRIMARY OBJECTIVE:
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2022-09737 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| UMCC 2022.038 | OTHER | University of Michigan Comprehensive Cancer Center | View | |
| UMI22-09-02 | OTHER | DCP | View | |
| P30CA046592 | NIH | None | https://reporter.nih.gov/quic… | View |
| UG1CA242632 | NIH | None | https://reporter.nih.gov/quic… | View |