Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 1:34 AM
Ignite Modification Date:
2025-12-25 @ 1:34 AM
NCT ID:
NCT05630794
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.
Study:
NCT05630794
Study Brief:
Protocol Section:
NCT05630794