NCT05828082

Testing the Effect of M1774 on Hard-to-Treat Refractory SPOP-mutant Prostate Cancer

A Phase 2 Study of M1774 in Refractory SPOP-Mutant Prostate Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests how well M1774 works in treating patients with prostate cancer that does not respond to treatment (refractory) and that has a mutation in the gene responsible for making the speckle type BTB/POZ protein (SPOP). M1774 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving M1774 may be able to shrink or stabilize refractory SPOP-mutant prostate cancer.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the response rate of the ATR inhibitor tuvusertib (M1774) in highly refractory prostate cancer. SECONDARY OBJECTIVES: I. To evaluate the overall survival (OS) of refractory SPOP-mutant prostate cancer patients receiving M1774. II. To evaluate the progression-free survival (PFS) of refractory SPOP-mutant prostate cancer patients receiving M1774. III. To evaluate the Common Terminology Criteria for Adverse Events (CTCAE) 5.0-defined adverse event (AE) rates of refractory SPOP-mutant prostate cancer patients receiving M1774. EXPLORATORY OBJECTIVE: I. To determine changes in SPOP-mutant circulating tumor deoxyribonucleic acid (ctDNA); SPOP-mutant prostate cancer-derived exosomes, and SPOP-, ATR-, and ATM-related gene signature changes on ATR inhibition, including RAC1, FDFT1, DHCR24, DHCR7, and MVD. OUTLINE: Patients receive tuvusertib orally (PO) every day (QD) on days 1-14 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET)/MRI, PET/CT or ultrasound (U/S) and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up every 6 months for 2 years.

Conditions

• Castration-Resistant Prostate Carcinoma
• Metastatic Castration-Resistant Prostate Carcinoma
• Refractory Prostate Carcinoma
• Stage IVB Prostate Cancer AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET/MRI or PET/CT
DRUG	Tuvusertib	Given PO
PROCEDURE	Ultrasound Imaging	Undergo U/S

Timeline

• Start date: 2023-10-16
• Primary completion: 2026-06-18
• Completion: 2026-06-18
• First posted: 2023-04-25
• Last updated: 2026-04-14

Locations

26 sites across 1 country: United States

Regulatory

• FDA-regulated drug study