難治性SPOP変異前立腺癌に対するM1774の効果の試験
難治性SPOP変異前立腺癌におけるM1774の第2相試験
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.
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究場所
-
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Arizona
-
Phoenix、Arizona、アメリカ、85054
- Mayo Clinic Hospital in Arizona
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California
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Orange、California、アメリカ、92868
- UC Irvine Health/Chao Family Comprehensive Cancer Center
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Florida
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Aventura、Florida、アメリカ、33180
- UM Sylvester Comprehensive Cancer Center at Aventura
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Coral Gables、Florida、アメリカ、33146
- UM Sylvester Comprehensive Cancer Center at Coral Gables
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Deerfield Beach、Florida、アメリカ、33442
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
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Jacksonville、Florida、アメリカ、32224-9980
- Mayo Clinic in Florida
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Miami、Florida、アメリカ、33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Illinois
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Shiloh、Illinois、アメリカ、62269
- Memorial Hospital East
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Kansas
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Kansas City、Kansas、アメリカ、66160
- University of Kansas Cancer Center
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Overland Park、Kansas、アメリカ、66211
- University of Kansas Hospital-Indian Creek Campus
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Westwood、Kansas、アメリカ、66205
- University of Kansas Hospital-Westwood Cancer Center
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Minnesota
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Rochester、Minnesota、アメリカ、55905
- Mayo Clinic in Rochester
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Missouri
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City of Saint Peters、Missouri、アメリカ、63376
- Siteman Cancer Center at Saint Peters Hospital
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Creve Coeur、Missouri、アメリカ、63141
- Siteman Cancer Center at West County Hospital
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St Louis、Missouri、アメリカ、63110
- Washington University School of Medicine
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St Louis、Missouri、アメリカ、63129
- Siteman Cancer Center-South County
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St Louis、Missouri、アメリカ、63136
- Siteman Cancer Center at Christian Hospital
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ、73104
- University of Oklahoma Health Sciences Center
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15232
- UPMC Hillman Cancer Center
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Texas
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Dallas、Texas、アメリカ、75390
- UT Southwestern/Simmons Cancer Center-Dallas
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Dallas、Texas、アメリカ、75237
- UT Southwestern Simmons Cancer Center - RedBird
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Fort Worth、Texas、アメリカ、76104
- UT Southwestern/Simmons Cancer Center-Fort Worth
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Richardson、Texas、アメリカ、75080
- UT Southwestern Clinical Center at Richardson/Plano
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Virginia
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Charlottesville、Virginia、アメリカ、22908
- University of Virginia Cancer Center
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Wisconsin
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Madison、Wisconsin、アメリカ、53792
- University of Wisconsin Carbone Cancer Center - University Hospital
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Madison、Wisconsin、アメリカ、53718
- University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
-
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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
他の名前：
Undergo MRI
他の名前：
Undergo biopsy
他の名前：
Undergo collection of blood samples
他の名前：
Given PO
他の名前：
Undergo PET/MRI or PET/CT
他の名前：
Undergo U/S
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Response rate
時間枠：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. |
Assessed up to 6 months from trial registration
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall Survival
時間枠：From trial registration until death due to any cause, assessed up to 2 years
|
From trial registration until death due to any cause |
From trial registration until death due to any cause, assessed up to 2 years
|
|
Progression Free Survival (PFS)
時間枠：From trial registration until the first indication of disease progression (or death), assessed up to 2 years
|
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
|
|
Incidence of adverse events (AE)
時間枠：Up to 2 years from registration date
|
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
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall SPOP-driven gene signature changes
時間枠：At cycle 1, day 9 and time of progression
|
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
|
協力者と研究者
捜査官
- 主任研究者：Jacob Orme、Dana-Farber - Harvard Cancer Center LAO
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- NCI-2023-03150
- UM1CA186709 (米国 NIH グラント/契約)
- 10603 (その他の識別子：CTEP)
- NCI-2023-03150 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- 10603 (その他の識別子：Dana-Farber - Harvard Cancer Center LAO)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
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.
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。