A Phase 2 Study of M1774 in Refractory SPOP-Mutant Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- Biospecimen Collection
- Conditions
- Not specified
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 20
- Locations
- 31
- Primary Endpoint
- Response rate
- Status
- Active, not recruiting
- Last Updated
- 18 days ago
Overview
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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)
Exclusion Criteria
- •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 M
- •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
Arms & Interventions
Treatment (tuvusertib)
Patients 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.
Intervention: Biospecimen Collection
Treatment (tuvusertib)
Patients 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.
Intervention: Biopsy Procedure
Treatment (tuvusertib)
Patients 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.
Intervention: Computed Tomography
Treatment (tuvusertib)
Patients 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.
Intervention: Magnetic Resonance Imaging
Treatment (tuvusertib)
Patients 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.
Intervention: Positron Emission Tomography
Treatment (tuvusertib)
Patients 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.
Intervention: Tuvusertib
Treatment (tuvusertib)
Patients 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.
Intervention: Ultrasound Imaging
Outcomes
Primary Outcomes
Response rate
Time Frame: Assessed up to 6 months from trial registration
Defined by the Prostate Cancer Working Group 3.0 criteria. Simon's two-stage design will be used.
Secondary Outcomes
- 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)