Testování účinku M1774 na těžko léčitelnou refrakterní SPOP-mutovanou rakovinu prostaty
Studie fáze 2 M1774 u refrakterního SPOP-mutovaného karcinomu prostaty
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.
Přehled studie
Postavení
Podmínky
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
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Arizona
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Phoenix, Arizona, Spojené státy, 85054
- Mayo Clinic Hospital in Arizona
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California
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Orange, California, Spojené státy, 92868
- UC Irvine Health/Chao Family Comprehensive Cancer Center
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Florida
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Aventura, Florida, Spojené státy, 33180
- UM Sylvester Comprehensive Cancer Center at Aventura
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Coral Gables, Florida, Spojené státy, 33146
- UM Sylvester Comprehensive Cancer Center at Coral Gables
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Deerfield Beach, Florida, Spojené státy, 33442
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
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Jacksonville, Florida, Spojené státy, 32224-9980
- Mayo Clinic in Florida
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Miami, Florida, Spojené státy, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Illinois
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Shiloh, Illinois, Spojené státy, 62269
- Memorial Hospital East
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Kansas
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Kansas City, Kansas, Spojené státy, 66160
- University of Kansas Cancer Center
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Overland Park, Kansas, Spojené státy, 66211
- University of Kansas Hospital-Indian Creek Campus
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Westwood, Kansas, Spojené státy, 66205
- University of Kansas Hospital-Westwood Cancer Center
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Minnesota
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Rochester, Minnesota, Spojené státy, 55905
- Mayo Clinic in Rochester
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Missouri
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City of Saint Peters, Missouri, Spojené státy, 63376
- Siteman Cancer Center at Saint Peters Hospital
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Creve Coeur, Missouri, Spojené státy, 63141
- Siteman Cancer Center at West County Hospital
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St Louis, Missouri, Spojené státy, 63110
- Washington University School of Medicine
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St Louis, Missouri, Spojené státy, 63129
- Siteman Cancer Center-South County
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St Louis, Missouri, Spojené státy, 63136
- Siteman Cancer Center at Christian Hospital
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Oklahoma
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Oklahoma City, Oklahoma, Spojené státy, 73104
- University of Oklahoma Health Sciences Center
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Pennsylvania
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Pittsburgh, Pennsylvania, Spojené státy, 15232
- UPMC Hillman Cancer Center
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Texas
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Dallas, Texas, Spojené státy, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
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Dallas, Texas, Spojené státy, 75237
- UT Southwestern Simmons Cancer Center - RedBird
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Fort Worth, Texas, Spojené státy, 76104
- UT Southwestern/Simmons Cancer Center-Fort Worth
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Richardson, Texas, Spojené státy, 75080
- UT Southwestern Clinical Center at Richardson/Plano
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Virginia
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Charlottesville, Virginia, Spojené státy, 22908
- University of Virginia Cancer Center
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Wisconsin
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Madison, Wisconsin, Spojené státy, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
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Madison, Wisconsin, Spojené státy, 53718
- University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
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Presence of SPOP mutations in prostate cancer cells, as indicated by Next Generation Sequencing (NGS)
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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
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Castrate-range testosterone (=< 50 ng/dL) after androgen deprivation therapy (ADT) or orchiectomy
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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
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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
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Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
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Absolute neutrophil count >= 1,500/mcL
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Platelets >= 100,000/mcL
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Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
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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)
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Creatinine =< 1.5 × ULN
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Creatinine clearance >= 60 mL/min
- Creatinine clearance should be measured if estimated glomerular filtration rate (eGFR) is > 60 mL/min
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Hemoglobin >= 9.0g/dL
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Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
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For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
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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
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Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
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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
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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
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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
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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
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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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: 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. |
Undergo CT
Ostatní jména:
Undergo MRI
Ostatní jména:
Undergo biopsy
Ostatní jména:
Undergo collection of blood samples
Ostatní jména:
Given PO
Ostatní jména:
Undergo PET/MRI or PET/CT
Ostatní jména:
Undergo U/S
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Response rate
Časové okno: Assessed up to 6 months from trial registration
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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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Overall Survival
Časové okno: From trial registration until death due to any cause, assessed up to 2 years
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From trial registration until death due to any cause |
From trial registration until death due to any cause, assessed up to 2 years
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Progression Free Survival (PFS)
Časové okno: From trial registration until the first indication of disease progression (or death), assessed up to 2 years
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The median PFS time, as well as a 95% confidence interval, will be constructed using the Kaplan-Meier method. |
From trial registration until the first indication of disease progression (or death), assessed up to 2 years
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Incidence of adverse events (AE)
Časové okno: Up to 2 years from registration date
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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. |
Up to 2 years from registration date
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Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Overall SPOP-driven gene signature changes
Časové okno: At cycle 1, day 9 and time of progression
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Overall SPOP-driven gene signature changes over the course of treatment will be measured by ribonucleic acid sequencing. These will include SPOP targets RAC1, FDFT1, DHCR24, DHCR7, and MVD. Changes in expression over time will be compared using a Wilcoxon signed-rank test. Changes in circulating SPOP-mutant fraction of circulating tumor deoxyribonucleic acid in responders will be compared to changes in non-responders using Student's t-test. |
At cycle 1, day 9 and time of progression
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Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Jacob Orme, Dana-Farber - Harvard Cancer Center LAO
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Urogenitální onemocnění
- Onemocnění genitálií
- Genitální novotvary, muži
- Urogenitální novotvary
- Novotvary podle místa
- Novotvary
- Onemocnění pohlavních orgánů, muž
- Onemocnění prostaty
- Mužská urogenitální onemocnění
- Novotvary prostaty
- Vyšetřovací techniky
- Klinické laboratorní techniky
- Diagnostické techniky a postupy
- Diagnóza
- Chirurgické postupy, operativní
- Cytologické techniky
- Cytodiagnosis
- Fyzické jevy
- Diagnostické techniky, chirurgické
- Techniky chemie, analytické
- Analýza spektra
- Záření
- Záření, neionizující
- Ultrazvukové vlny
- Zvuk
- Biopsie
- Manipulace se vzorkem
- Magnetická rezonanční spektroskopie
- Šokové vlny s vysokou energií
Další identifikační čísla studie
- NCI-2023-03150
- UM1CA186709 (Grant/smlouva NIH USA)
- 10603 (Jiný identifikátor: CTEP)
- NCI-2023-03150 (Identifikátor registru: CTRP (Clinical Trial Reporting Program))
- 10603 (Jiný identifikátor: Dana-Farber - Harvard Cancer Center LAO)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
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.
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
produkt vyrobený a vyvážený z USA
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