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.
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
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
Sequential
Lutetium Lu 177 Vipivotide Tetraxetan
DrugGiven IV
Cell-free Circulating Tumor DNA Assay
Procedure/SurgeryUndergo ctDNA TF testing
Computed Tomography
Procedure/SurgeryUndergo CT
Docetaxel
DrugGiven IV
PSMA PET Scan
Procedure/SurgeryUndergo PSMA PET
Single Photon Tomography and Computed Tomography Scan
Procedure/SurgeryUndergo SPECT/CT
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
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.
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.
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.
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.
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.
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.
Click on the lead sponsor to view all of their trials.
University of Washington
Lead sponsor
Institute for Prostate Cancer Research (IPCR)
Collaborator
