Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Patients receive tuvusertib PO QD on days 1-14. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy, MRI, CT, PET/MRI, PET/CT or U/S and collection of blood samples throughout the trial.

Biopsy

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Tuvusertib

Ultrasound Imaging

Site Public Contact

Jacob Orme

Arash Rezazadeh Kalebasty

Janaki N. Sharma

Melissa A. Reimers

Rahul A. Parikh

Adanma Anji Ayanambakkam Attanathi

Priyanka V. Chablani

Kevin D. Courtney

Paul V. Viscuse

Glenn Liu

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.

PRIMARY OBJECTIVE:

I. To evaluate the response rate of tuvusertib (ATR inhibitor M1774) in highly refractory prostate cancer.

SECONDARY OBJECTIVES:

I. To evaluate the overall survival (OS) of refractory SPOP-mutant prostate cancer patients receiving tuvusertib (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) 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. 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.

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

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Overall SPOP-driven gene signature changes over the course of treatment will be measured by ribonucleic acid sequencing (RNAseq). These will include SPOP targets RAC1, FDFT1, DHCR24, DHCR7, and MVD. Changes in expression over time will be compared using a Wilcoxon signed-rank test. Changes in circulating SPOP-mutant fraction of circulating tumor deoxyribonucleic acid (ctDNA) in responders will be compared to changes in non-responders using Student's t-test.

Defined by the Prostate Cancer Working Group 3.0 (PCWG3) criteria. Simon's two-stage design will be used.

From trial registration until death due to any cause

The median PFS time, as well as a 95% confidence interval, will be constructed using the Kaplan-Meier method.

Maximum grade AE's will be summarized using simple counting statistics in a tabular fashion. This will be done both with and without regard to treatment attribution. Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Spots Global Cancer Trial Database for refractory prostate carcinoma