Trial Title:
Testing the Effect of M1774 on Hard-to-Treat Refractory SPOP-mutant Prostate Cancer
NCT ID:
NCT05828082
Condition:
Refractory Prostate Carcinoma
Conditions: Official terms:
Prostatic Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (tuvusertib)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Correlative studies
Arm group label:
Treatment (tuvusertib)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (tuvusertib)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (tuvusertib)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/MRI or PET/CT
Arm group label:
Treatment (tuvusertib)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Drug
Intervention name:
Tuvusertib
Description:
Given PO
Arm group label:
Treatment (tuvusertib)
Other name:
ATR Kinase Inhibitor M1774
Other name:
M 1774
Other name:
M-1774
Other name:
M1774
Intervention type:
Procedure
Intervention name:
Ultrasound Imaging
Description:
Undergo U/S
Arm group label:
Treatment (tuvusertib)
Other name:
2-Dimensional Grayscale Ultrasound Imaging
Other name:
2-Dimensional Ultrasound Imaging
Other name:
2D-US
Other name:
Ultrasonography
Other name:
Ultrasound
Other name:
Ultrasound Test
Other name:
Ultrasound, Medical
Other name:
US
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 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.
Criteria for 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]) and
alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase [SGPT]) =< 3 x
institutional 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
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 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
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic Hospital in Arizona
Address:
City:
Phoenix
Zip:
85054
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
855-776-0015
Investigator:
Last name:
Jacob Orme
Email:
Principal Investigator
Facility:
Name:
UC Irvine Health/Chao Family Comprehensive Cancer Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-827-8839
Email:
ucstudy@uci.edu
Investigator:
Last name:
Arash Rezazadeh Kalebasty
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Aventura
Address:
City:
Aventura
Zip:
33180
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
954-461-2180
Investigator:
Last name:
Janaki N. Sharma
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Coral Gables
Address:
City:
Coral Gables
Zip:
33146
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Janaki N. Sharma
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Address:
City:
Deerfield Beach
Zip:
33442
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Janaki N. Sharma
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
855-776-0015
Investigator:
Last name:
Jacob Orme
Email:
Principal Investigator
Facility:
Name:
University of Miami Miller School of Medicine-Sylvester Cancer Center
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Janaki N. Sharma
Email:
Principal Investigator
Facility:
Name:
Memorial Hospital East
Address:
City:
Shiloh
Zip:
62269
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
314-747-9912
Email:
dschwab@wustl.edu
Investigator:
Last name:
Melissa A. Reimers
Email:
Principal Investigator
Facility:
Name:
University of Kansas Cancer Center
Address:
City:
Kansas City
Zip:
66160
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Rahul A. Parikh
Email:
Principal Investigator
Facility:
Name:
University of Kansas Hospital-Indian Creek Campus
Address:
City:
Overland Park
Zip:
66211
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Rahul A. Parikh
Email:
Principal Investigator
Facility:
Name:
University of Kansas Hospital-Westwood Cancer Center
Address:
City:
Westwood
Zip:
66205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Rahul A. Parikh
Email:
Principal Investigator
Facility:
Name:
Dana-Farber - Harvard Cancer Center LAO
Address:
City:
Boston
Zip:
02115
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jacob Orme
Phone:
507-284-2511
Email:
orme.jacob@mayo.edu
Investigator:
Last name:
Jacob Orme
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
855-776-0015
Investigator:
Last name:
Jacob Orme
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at West County Hospital
Address:
City:
Creve Coeur
Zip:
63141
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Melissa A. Reimers
Email:
Principal Investigator
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Melissa A. Reimers
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center-South County
Address:
City:
Saint Louis
Zip:
63129
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Melissa A. Reimers
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at Christian Hospital
Address:
City:
Saint Louis
Zip:
63136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Melissa A. Reimers
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at Saint Peters Hospital
Address:
City:
Saint Peters
Zip:
63376
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Melissa A. Reimers
Email:
Principal Investigator
Facility:
Name:
University of Oklahoma Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
405-271-8777
Email:
ou-clinical-trials@ouhsc.edu
Investigator:
Last name:
Adanma Anji Ayanambakkam Attanathi
Email:
Principal Investigator
Facility:
Name:
University of Pittsburgh Cancer Institute (UPCI)
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
412-647-8073
Investigator:
Last name:
Priyanka V. Chablani
Email:
Principal Investigator
Facility:
Name:
UT Southwestern Simmons Cancer Center - RedBird
Address:
City:
Dallas
Zip:
75237
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
214-648-7097
Email:
canceranswerline@utsouthwestern.edu
Investigator:
Last name:
Kevin D. Courtney
Email:
Principal Investigator
Facility:
Name:
UT Southwestern/Simmons Cancer Center-Dallas
Address:
City:
Dallas
Zip:
75390
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
214-648-7097
Email:
canceranswerline@UTSouthwestern.edu
Investigator:
Last name:
Kevin D. Courtney
Email:
Principal Investigator
Facility:
Name:
UT Southwestern/Simmons Cancer Center-Fort Worth
Address:
City:
Fort Worth
Zip:
76104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
214-648-7097
Email:
canceranswerline@UTSouthwestern.edu
Investigator:
Last name:
Kevin D. Courtney
Email:
Principal Investigator
Facility:
Name:
UT Southwestern Clinical Center at Richardson/Plano
Address:
City:
Richardson
Zip:
75080
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
972-669-7044
Email:
Suzanne.cole@utsouthwestern.edu
Investigator:
Last name:
Kevin D. Courtney
Email:
Principal Investigator
Facility:
Name:
University of Virginia Cancer Center
Address:
City:
Charlottesville
Zip:
22908
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
434-243-6303
Email:
uvacancertrials@hscmail.mcc.virginia.edu
Investigator:
Last name:
Paul V. Viscuse
Email:
Principal Investigator
Facility:
Name:
University of Wisconsin Carbone Cancer Center - University Hospital
Address:
City:
Madison
Zip:
53792
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-622-8922
Email:
clinicaltrials@cancer.wisc.edu
Investigator:
Last name:
Glenn Liu
Email:
Principal Investigator
Start date:
October 16, 2023
Completion date:
April 25, 2025
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05828082
