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
3 other identifiers
interventional
20
1 country
26
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Oct 2023
Typical duration for phase_2
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 22, 2023
CompletedFirst Posted
Study publicly available on registry
April 25, 2023
CompletedStudy Start
First participant enrolled
October 16, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2027
July 31, 2026
May 1, 2026
3.2 years
April 22, 2023
July 30, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Response rate
Defined by the Prostate Cancer Working Group 3.0 criteria. Simon's two-stage design will be used.
Assessed up to 6 months from trial registration
Secondary Outcomes (3)
Overall Survival
From trial registration until death due to any cause, assessed up to 2 years
Progression Free Survival (PFS)
From trial registration until the first indication of disease progression (or death), assessed up to 2 years
Incidence of adverse events (AE)
Up to 2 years from registration date
Other Outcomes (1)
Overall SPOP-driven gene signature changes
At cycle 1, day 9 and time of progression
Study Arms (1)
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.
Interventions
Undergo CT
Undergo MRI
Undergo PET/MRI or PET/CT
Given PO
Undergo U/S
Undergo collection of blood samples
Eligibility Criteria
You may qualify if:
- 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%)
- 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 Ă— 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
- +8 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
UT Southwestern Simmons Cancer Center - RedBird
Dallas, Texas, 75237, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth, Texas, 76104, United States
UT Southwestern Clinical Center at Richardson/Plano
Richardson, Texas, 75080, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jacob Orme
Dana-Farber - Harvard Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 22, 2023
First Posted
April 25, 2023
Study Start
October 16, 2023
Primary Completion (Estimated)
January 1, 2027
Study Completion (Estimated)
January 1, 2027
Last Updated
July 31, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
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.