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Castration-Resistant Prostate CarcinomaPhase 2NCT05828082

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

A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Castration-Resistant Prostate Carcinoma and Metastatic Castration-Resistant Prostate Carcinoma, run by National Cancer Institute (NCI) at 26 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Biopsy Procedure, Biospecimen Collection and Computed Tomography
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
26 sitesUnited States
Study dates
16 Oct 2023to 1 Jan 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Presence of SPOP mutations in prostate cancer cells, as indicated by Next Generation Sequencing (NGS)
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with CT scan, MRI, or calipers by clinical exam
  • Castrate-range testosterone (=< 50 ng/dL) after androgen deprivation therapy (ADT) or orchiectomy
  • Prior treatment with second generation anti-androgen (2GAA) and taxane- or lutetium-based therapy. More than one kind of prior treatment with 2GAA and taxane - or lutetium-based therapies is also acceptable
  • Age >= 18 years. Because no dosing or adverse event data are currently available on the use of M1774 in patients < 18 years of age, children are excluded from this study
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
Show all 23Show fewer
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase [SGPT]) =< 3 x institutional upper limit of normal (ULN)
  • Creatinine =< 1.5 × ULN
  • Creatinine clearance >= 60 mL/min
  • Creatinine clearance should be measured if estimated glomerular filtration rate (eGFR) is > 60 mL/min
  • Hemoglobin >= 9.0g/dL
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
  • Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • The effects of M1774 on the developing human fetus are unknown. For this reason and because ATR inhibitors may be teratogenic (Musson et al., 2022), women of child-bearing potential who are partners of men enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to the study, for the duration of study participation, and 6 months after completion of M1774 administration. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately. Men enrolled on this study must agree to use adequate contraception prior to study entry, for the duration of study participation, and 3 months after completion of M1774 administration
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Who cannot join

  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
  • Patients who are receiving any other investigational agents
  • Patients with uncontrolled intercurrent illness
  • Patients who cannot discontinue proton pump inhibitors (PPIs). H2 receptor antagonists will not be permitted within 12 hours before dosing of M1774 and until 2 hours after dosing of M1774. Antacids will not be permitted within 2 hours before and 2 hours after administration of M1774
  • Patients who cannot discontinue drugs that are strong inhibitors of CYP3A4 or CYP1A2
  • Patients who cannot discontinue drugs that are hMATE1 or hMATE2-Ksubstrates
  • Patients with a baseline QC interval > 470 msec

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

United States26 sites

  • UM Sylvester Comprehensive Cancer Center at Aventura

    Aventura, Florida, 33180

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • UT Southwestern Simmons Cancer Center - RedBird

    Dallas, Texas, 75237

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • UT Southwestern/Simmons Cancer Center-Fort Worth

    Fort Worth, Texas, 76104

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

    Madison, Wisconsin, 53718

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • University of Kansas Hospital-Indian Creek Campus

    Overland Park, Kansas, 66211

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UT Southwestern Clinical Center at Richardson/Plano

    Richardson, Texas, 75080

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Memorial Hospital East

    Shiloh, Illinois, 62269

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Biopsy Procedure, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Positron Emission Tomography
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood samples

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/MRI or PET/CT

  • TuvusertibDrug

    Also called ATR Kinase Inhibitor M1774, M 1774, M-1774, M1774

    Given PO

  • Ultrasound ImagingProcedure or surgery

    Also called 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography

    Undergo U/S

Study groups in NCT05828082
Study groupRoleWhat they receive
Treatment (tuvusertib)ExperimentalPatients receive tuvusertib PO 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, MRI, CT, PET/MRI, PET/CT or U/S and collection of blood samples throughout the trial.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Tuvusertib; Procedure: Ultrasound Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response rate

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

    Measured: Assessed up to 6 months from trial registration

Secondary outcomes (3)

  1. Overall Survival

    From trial registration until death due to any cause

    Measured: From trial registration until death due to any cause, assessed up to 2 years

  2. Progression Free Survival (PFS)

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

    Measured: From trial registration until the first indication of disease progression (or death), assessed up to 2 years

  3. 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.

    Measured: Up to 2 years from registration date

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2023
  2. Study start16 Oct 2023
  3. Primary completion1 Jan 2027 (estimated)
  4. Study completion1 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05828082
Sponsor's protocol ID
NCI-2023-03150
Other IDs
NCI-2023-03150, 10603, 10603, UM1CA186709
Status last verified
May 2026
First submitted
22 Apr 2023
Last updated
31 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Castration-Resistant Prostate Carcinoma and Metastatic Castration-Resistant Prostate Carcinoma, run by National Cancer Institute (NCI) at 26 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response rate (time frame: Assessed up to 6 months from trial registration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05828082.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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