Measuring Circulating Tumor Deoxyribonucleic Acid Tumor Fraction to Guide Early 177Lu-PSMA-617 Treatment Discontinuation in Patients With Metastatic Castration-Resistant Prostate Cancer, DYNAMO Trial
2026年8月26日 更新者：University of Washington
Dynamic Assessments of Molecular Response to Guide Early 177Lu-PSMA-617 Treatment Discontinuation: The DYNAMO Study
This clinical trial studies whether measuring circulating tumor deoxyribonucleic acid (ctDNA) tumor fraction (TF) can be used to help guide the early stopping (discontinuation) of lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) in patients with castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic).
Many types of tumors tend to lose cells or release different types of cellular products including their deoxyribonucleic acid, which is referred to as ctDNA, into the bloodstream before changes can be seen on scans.
Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for the disease to grow, spread, or get worse or come back after a period of improvement.
ctDNA TF is a type of ctDNA measurement.
Research has shown ctDNA TF may be a promising way to predict which patients will respond to 177Lu-PSMA-617 treatment.
Measuring ctDNA TF may help doctors identify which patients may benefit from changing treatments sooner, which may be an effective way to guide early 177Lu-PSMA-617 treatment discontinuation in patients with metastatic castration-resistant prostate cancer.
調査の概要
状態
状態
募集
条件
条件
介入・治療
介入・治療
詳細な説明
OUTLINE:
CYCLES 1 AND 2: Patients receive 177Lu-PSMA-617 intravenously (IV) over 20-30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection with ctDNA TF testing at baseline and C2D1. Patients with undetectable ctDNA TF (< 3%) on C2D1 continue to receive 177Lu-PSMA-617 as above in the absence of disease progression or unacceptable toxicity. Patients with detectable ctDNA TF (≥ 3%) on C2D1 are randomized to 1 of 2 arms.
CYCLE 3+ ARM I: Starting with cycle 3, patients receive 177Lu-PSMA-617 IV over 20-30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
CYCLE 3+ ARM II: Starting with cycle 3, patients receive docetaxel IV on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo PSMA positron emission tomography (PET) during screening, single photon emission computed tomography (SPECT)/computed tomography (CT) on study, and additional blood sample collection as well as CT throughout the study.
After completion of study treatment, patients are followed up every 12 weeks for up to 1 year.
研究の種類
研究の種類
介入
入学 (推定)
入学
64
段階
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
研究連絡先
- 名前：Michael Schweizer, MD
- 電話番号：206-606-6252
- メール：schweize@uw.edu
研究場所
-
-
Washington
-
Seattle、Washington、アメリカ、98109
- 募集
- Fred Hutch/University of Washington Cancer Consortium
-
主任研究者：
- Michael Schweizer, MD
-
コンタクト：
- Michael Schweizer, MD
- 電話番号：206-606-6252
- メール：schweize@uw.edu
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
Inclusion Criteria:
- Willing and able to provide informed consent
- Adult males ≥ 18 years age
- History of histologically confirmed adenocarcinoma of the prostate without evidence of neuroendocrine or small cell differentiation. If histology is not available, patients must have metastatic disease typical of prostate cancer (i.e., involving bone or pelvic lymph nodes or para-aortic lymph nodes)
- Evidence of metastatic disease on bone scan or CT scan
Patient must have evidence of castration- resistant prostate cancer as evidenced by PSA progression (per Prostate Cancer Working Group 3 [PCWG3] criteria) and a castrate serum testosterone level (i.e., ≤ 50 mg/dL)
- Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Prior treatment and progression on at least one androgen receptor pathway inhibitor (ARPI), in either castration-sensitive or castration-resistant setting
- Eligible for treatment with either 177Lu-PSMA-617 or docetaxel as per their respective Food and Drug Administration (FDA) labels
- Absolute neutrophil count ≥ 1.5 x 10^9/L
- Platelet count ≥ 100 x 10^9/L
- Hemoglobin ≥ 9 g/dL
- Creatinine clearance ≥ 50 ml/min (calculated by Cockcroft-Gault formula)
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome (direct bilirubin ≤ 1.5 x ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, unless liver metastases are present in which case they must be ≤ 5 x ULN. For patients with known Gilbert's Syndrome they must be ≤ 3 x ULN
- Able to comply with study requirements including provision of peripheral blood samples at specified time points for correlative studies
Exclusion Criteria:
- Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition that could interfere with patient safety or provision of informed consent to participate in this study
- Evidence of metastatic neuroendocrine/small cell prostate cancer (NEPC). Note: baseline biopsy is not required
- Patients receiving any systemic therapy (aside from a luteinizing hormone-releasing hormone [LHRH] analogue) or radiotherapy within 2 weeks prior to study treatment
- Persistent toxicities (CTCAE grade > 2) from prior cancer therapy, excluding alopecia and stable neuropathy
- Patients considered a poor medical risk due to a serious, uncontrolled medical disorder or active, uncontrolled infection. Examples include, but are not limited to uncontrolled seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
- Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and a CD4 count < 200
- Patients with known active hepatitis (i.e. hepatitis B or C). Prior hepatitis C infection is allowed as long as polymerase chain reaction (PCR) is negative
- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
- Serious cardiac disorder, including but not limited to uncontrolled ventricular arrhythmia, recent (within 12 months) myocardial infarction, resting electrocardiogram (ECG) indicating Fridericia's corrected QT interval prolongation > 500ms, or congenital long QT syndrome
- Prior systemic chemotherapy with taxane chemotherapy, including in hormone sensitive setting (e.g. docetaxel or cabazitaxel)
Brain metastases or active epidural disease (treated epidural disease is permitted)
- Note: baseline brain imaging is not required
- Contraindication to prednisone therapy including poorly controlled diabetes mellitus
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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：ランダム化
- 介入モデル：順次割り当て
- マスキング：なし（オープンラベル）
アーム数
3
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
他の：Cycles 1 and 2 (177Lu-PSMA-617, ctDNA testing)
Patients receive 177Lu-PSMA-617 IV over 20-30 minutes on day 1 of each cycle.
Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood sample collection with ctDNA TF testing at baseline and C2D1.
Patients with undetectable ctDNA TF (< 3%) on C2D1 continue to receive 177Lu-PSMA-617 as above in the absence of disease progression or unacceptable toxicity.
Patients with detectable ctDNA TF (≥ 3%) on C2D1 are randomized to 1 of 2 arms.
Additionally, patients undergo PSMA PET during screening, SPECT/CT on study, and additional blood sample collection as well as CT throughout the study.
|
CTを受ける
他の名前：
採血を受ける
他の名前：
PSMA PETを受ける
他の名前：
ギヴンIV
他の名前：
SPECT/CTを受ける
他の名前：
Undergo ctDNA TF testing
他の名前：
|
|
アクティブコンパレータ：Cycle 3+ Arm I (177Lu-PSMA-617)
Starting with cycle 3, patients receive 177Lu-PSMA-617 IV over 20-30 minutes on day 1 of each cycle.
Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo PSMA PET during screening, SPECT/CT on study, and additional blood sample collection as well as CT throughout the study.
|
CTを受ける
他の名前：
採血を受ける
他の名前：
PSMA PETを受ける
他の名前：
ギヴンIV
他の名前：
SPECT/CTを受ける
他の名前：
|
|
アクティブコンパレータ：Cycle 3+ Arm II (docetaxel)
Starting with cycle 3, patients receive docetaxel IV on day 1 of each cycle.
Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo PSMA PET during screening, SPECT/CT on study, and additional blood sample collection as well as CT throughout the study.
|
与えられた IV
他の名前：
CTを受ける
他の名前：
採血を受ける
他の名前：
PSMA PETを受ける
他の名前：
SPECT/CTを受ける
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
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number and proportion among those recruited with detectable circulating tumor deoxyribonucleic acid (ctDNA) tumor fraction who undergo randomization
時間枠：Up to 2 cycles (Cycle length = 6 weeks)
|
Will be analyzed descriptively.
Among patients who initiate lutetium Lu 177 vipivotide tetraxetan and undergo cycle (C) 2 day (D) 1 ctDNA tumor fraction assessment, the number (and proportion among those recruited) with detectable ctDNA tumor fraction who undergo randomization will be reported with a two-sided 95% Wilson confidence interval.
|
Up to 2 cycles (Cycle length = 6 weeks)
|
|
Number of patients screened, enrolled, evaluable for C2D1 ctDNA tumor fraction and for who cycle 3 is administered
時間枠：Up to cycle 3 administration (Cycle length = 6 weeks)
|
Will report the number of patients screened, enrolled, evaluable for C2D1 (week 13) ctDNA tumor fraction, classified as having detectable versus undetectable ctDNA tumor fraction, and for who cycle 3 is administered.
Reasons for failure to undergo C1D28 ctDNA assessment or randomization will be tabulated.
|
Up to cycle 3 administration (Cycle length = 6 weeks)
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Radiographic progression free survival (PFS)
時間枠：From randomization to disease progression, clinical progression, or death, whichever occurs first, assessed up to 1 year
|
Will be estimated in the subset of patients who undergo randomization.
Disease progression assessed per modified Response Evaluation Criteria in Solid Tumors criteria or the Prostate Cancer Working Group 3 criteria for bone lesions.
Clinical progression as determined by the treating physician.
Will be estimated using the Kaplan-Meier method.
Differences between groups will be evaluated using the log-rank test and the hazard ratio from a Cox regression model with treatment group as the predictor variable following assessment of proportional hazards.
Will also visualize PFS point estimates and 95% confidence interval (CI) bands over time and report median and 95% CIs of PFS for each group.
|
From randomization to disease progression, clinical progression, or death, whichever occurs first, assessed up to 1 year
|
|
Overall survival
時間枠：From the start of treatment until death from any cause, assessed up to 1 year
|
Will be estimated in the subset of patients who undergo randomization.
Will be estimated using the Kaplan-Meier method.
Differences between groups will be evaluated using the log-rank test and the hazard ratio from a Cox regression model with treatment group as the predictor variable following assessment of proportional hazards.
|
From the start of treatment until death from any cause, assessed up to 1 year
|
|
Prostate-specific antigen (PSA) PFS
時間枠：From the start of treatment until PSA progression, assessed up to 1 year
|
Will be estimated in the subset of patients who undergo randomization.
Will be estimated using the Kaplan-Meier method.
Differences between groups will be evaluated using the log-rank test and the hazard ratio from a Cox regression model with treatment group as the predictor variable following assessment of proportional hazards.
|
From the start of treatment until PSA progression, assessed up to 1 year
|
|
Proportion of patients with a ≥ 50% decline in PSA from baseline (PSA50) response rate
時間枠：Up to 1 year
|
Will be estimated in the subset of patients who undergo randomization.
Will be reported as a percentage with 95% CI calculated using Wilson's method.
Changes in PSA from baseline, with patients achieving PSA50, may be visualized using waterfall plots.
|
Up to 1 year
|
|
Duration of response
時間枠：From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 1 year
|
Will be estimated in the subset of patients who undergo randomization.
|
From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 1 year
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
協力者
協力者
捜査官
捜査官
- 主任研究者：Michael Schweizer, MD、Fred Hutch/University of Washington Cancer Consortium
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
研究開始
2026年10月1日
一次修了 (推定)
一次修了
2029年7月5日
研究の完了 (推定)
研究の完了
2029年7月5日
試験登録日
最初に提出
最初に提出
2026年6月25日
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
2026年7月6日
最初の投稿 (実際)
最初の投稿
2026年7月13日
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
2026年8月27日
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
2026年8月26日
最終確認日
最終確認日
2026年7月1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
その他の研究ID番号
- RG1126448
- NCI-2026-03971 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- FHIRB0021269 (その他の識別子：Fred Hutch/University of Washington Cancer Consortium)
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?
いいえ
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
はい
米国FDA規制機器製品の研究
はい
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。