Metastatic Castration-Resistant Prostate AdenocarcinomaPhase 2NCT07698535
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
A Phase 2 study testing Lutetium Lu 177 Vipivotide Tetraxetan, Cell-free Circulating Tumor DNA Assay and Computed Tomography in people with Metastatic Castration-Resistant Prostate Adenocarcinoma and Stage IVB Prostate Cancer AJCC v8, run by University of Washington at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castration-Resistant Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8
- What is being tested?
- Lutetium Lu 177 Vipivotide Tetraxetan, Cell-free Circulating Tumor DNA Assay and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2026to 5 Jul 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 16Show fewer
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
Michael Schweizer, MD, 206-606-6252, schweize@uw.edu
Michael Schweizer, MD
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Metastatic Castration-Resistant Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8
- Being tested
- Lutetium Lu 177 Vipivotide Tetraxetan, Cell-free Circulating Tumor DNA Assay, Computed Tomography, Docetaxel, PSMA PET Scan
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lutetium Lu 177 Vipivotide TetraxetanDrug
Also called 177Lu-labeled PSMA-617, 177Lu-PSMA-617, Pluvicto, AAA 617
Given IV
Cell-free Circulating Tumor DNA AssayProcedure or surgery
Also called ctDNA Assay, Signatera
Undergo ctDNA TF testing
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
DocetaxelDrug
Also called Docecad, RP 56976, RP-56976, RP56976
Given IV
PSMA PET ScanProcedure or surgery
Also called Prostate-specific Membrane Antigen PET, PSMA PET, PSMA-Positron emission tomography
Undergo PSMA PET
Single Photon Tomography and Computed Tomography ScanProcedure or surgery
Also called SPECT/CT, SPECT/CT SCAN
Undergo SPECT/CT
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
| Study group | Role | What they receive |
|---|---|---|
| Cycles 1 and 2 (177Lu-PSMA-617, ctDNA testing) | Other | 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. Receives: Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Procedure: Cell-free Circulating Tumor DNA Assay; Procedure: Computed Tomography; Procedure: PSMA PET Scan; Procedure: Single Photon Tomography and Computed Tomography Scan; Procedure: Biospecimen Collection |
| Cycle 3+ Arm I (177Lu-PSMA-617) | Active comparator | 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. Receives: Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Procedure: Computed Tomography; Procedure: PSMA PET Scan; Procedure: Single Photon Tomography and Computed Tomography Scan; Procedure: Biospecimen Collection |
| Cycle 3+ Arm II (docetaxel) | Active comparator | 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. Receives: Procedure: Computed Tomography; Drug: Docetaxel; Procedure: PSMA PET Scan; Procedure: Single Photon Tomography and Computed Tomography Scan; Procedure: Biospecimen Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and proportion among those recruited with detectable circulating tumor deoxyribonucleic acid (ctDNA) tumor fraction who undergo randomization
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.
Measured: 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
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.
Measured: Up to cycle 3 administration (Cycle length = 6 weeks)
Secondary outcomes (5)
Radiographic progression free survival (PFS)
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.
Measured: From randomization to disease progression, clinical progression, or death, whichever occurs first, assessed up to 1 year
Overall survival
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.
Measured: From the start of treatment until death from any cause, assessed up to 1 year
Prostate-specific antigen (PSA) PFS
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.
Measured: 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
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.
Measured: Up to 1 year
Duration of response
Will be estimated in the subset of patients who undergo randomization.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2026
- Study start15 Nov 2026 (estimated)
- Primary completion5 Jul 2029 (estimated)
- Study completion5 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castration-Resistant Prostate AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- Institute for Prostate Cancer Research (IPCR)
- Responsible party
- Sponsor
- Investigators
- Michael Schweizer, MD, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07698535
- Sponsor's protocol ID
- RG1126448
- Other IDs
- NCI-2026-03971, FHIRB0021269
- Status last verified
- Jul 2026
- First submitted
- 25 Jun 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No