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 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Undergo biopsy
Undergo collection of blood samples
Undergo CT
Undergo MRI
Undergo PET/MRI or PET/CT
Given PO
Undergo U/S
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
Response rate
Defined by the Prostate Cancer Working Group 3.0 criteria. Simon's two-stage design will be used.
Time frame: Assessed up to 6 months from trial registration
Overall Survival
From trial registration until death due to any cause
Time frame: From trial registration until death due to any cause, assessed up to 2 years
Progression Free Survival (PFS)
The median PFS time, as well as a 95% confidence interval, will be constructed using the Kaplan-Meier method.
Time frame: From trial registration until the first indication of disease progression (or death), assessed up to 2 years
Incidence of adverse events (AE)
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 version 5.0.
Time frame: Up to 2 years from registration date
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Mayo Clinic in Florida
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Memorial Hospital East
Shiloh, Illinois, United States
University of Kansas Cancer Center
Kansas City, Kansas, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, United States
...and 16 more locations