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Clinical Trial Summary

This phase I trial tests the safety, side effects, and best dose of Akt/ERK Inhibitor ONC201 (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.


Clinical Trial Description

PRIMARY OBJECTIVE: I. To determine the optimal cancer preventive dose of ONC201 defined as the lowest dose with less than or equal to 16.67% of participants experiencing unacceptable toxicity and simultaneously resulting in a statistically significant increase in human adenoma tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression. SECONDARY OBJECTIVES: I. To determine the lowest dose of ONC201 with less than or equal to 16.67% of participants experiencing unacceptable toxicity and simultaneously resulting in a statistically significant increase in normal human mucosa TRAIL expression. II. To evaluate the safety and tolerability of multiple ascending doses of ONC201 when administered weekly and every 3 weeks in participants with familial adenomatous polyposis (FAP) or with multiple adenomas. EXPLORATORY OBJECTIVES: I. To evaluate the impact of ONC201 on: Ia. Cytokine/immune response profiles (with attention to IL-10, IL-17A, 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 killers (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 12 weeks. Patients also undergo collection of blood, tissue biopsy, and sigmoidoscopy/colonoscopy throughout the study. After completion of study treatment, patients are followed up for 4 weeks. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05630794
Study type Interventional
Source National Cancer Institute (NCI)
Contact
Status Not yet recruiting
Phase Phase 1
Start date October 8, 2024
Completion date January 1, 2028

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