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
Dynamic Assessments of Molecular Response to Guide Early 177Lu-PSMA-617 Treatment Discontinuation: The DYNAMO Study
3 other identifiers
interventional
64
1 country
1
Brief 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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Dec 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 25, 2026
CompletedFirst Posted
Study publicly available on registry
July 13, 2026
CompletedStudy Start
First participant enrolled
December 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
July 5, 2029
Study Completion
Last participant's last visit for all outcomes
July 5, 2029
July 17, 2026
July 1, 2026
2.6 years
June 25, 2026
July 15, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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.
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.
Up to cycle 3 administration (Cycle length = 6 weeks)
Secondary Outcomes (5)
Radiographic progression free survival (PFS)
From randomization to disease progression, clinical progression, or death, whichever occurs first, assessed up to 1 year
Overall survival
From the start of treatment until death from any cause, assessed up to 1 year
Prostate-specific antigen (PSA) PFS
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
Up to 1 year
Duration of response
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
Study Arms (3)
Cycles 1 and 2 (177Lu-PSMA-617, ctDNA testing)
OTHERPatients 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.
Cycle 3+ Arm I (177Lu-PSMA-617)
ACTIVE COMPARATORStarting 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.
Cycle 3+ Arm II (docetaxel)
ACTIVE COMPARATORStarting 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.
Interventions
Given IV
Undergo ctDNA TF testing
Undergo CT
Given IV
Undergo PSMA PET
Undergo SPECT/CT
Undergo blood sample collection
Eligibility Criteria
You may qualify if:
- 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
- +1 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Schweizer, MD
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 25, 2026
First Posted
July 13, 2026
Study Start (Estimated)
December 1, 2026
Primary Completion (Estimated)
July 5, 2029
Study Completion (Estimated)
July 5, 2029
Last Updated
July 17, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will not share