This phase II trial tests how well 177Lu-PSMA-617 works in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that remains despite treatment (resistant). Lutetium Lu 177 (177Lu), the radioactive (tracer) component being delivered by prostate-specific membrane antigen (PSMA)-617, has physical properties that make it ideal radionuclide (imaging tests that uses a small dose tracer) for treatment of metastatic castrate-resistant prostate cancer (mCRPC). 177Lu-PSMA-617 works by binding to prostate cancer cells and inducing damage to deoxyribonucleic acid (DNA) inside prostate cancer cells. Giving 177Lu-PSMA-617 may improve treatment outcomes for patients with mCRPC.
Patients must have the ability to understand and sign an approved informed consent.
Patients must have the ability to understand and comply with all protocol requirements.
Patients must be ≥ 18 years of age.
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation within 6 months prior to treatment day 1. Previous PSMA-targeted radioligand therapy is not allowed.
Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 30 days prior to treatment day 1.
Concurrent bone strengthening agents such as bisphosphonates (such as zolendronic acid) and RANKL inhibitors (such as denosumab) are allowed.
Any investigational agents within 30 days prior to treatment day 1.
Single group
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Scan
Procedure/SurgeryUndergo bone scan
Computed Tomography
Procedure/SurgeryUndergo SPECT/CT and CT
Lutetium Lu 177 Vipivotide Tetraxetan
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
PSMA PET-CT Scan
Procedure/SurgeryUndergo PSMA PET/CT
Questionnaire Administration
Other interventionAncillary studies
Single Photon Emission Computed Tomography
Procedure/SurgeryUndergo SPECT/CT
Prostate-specific antigen (PSA) progression-free survival (PFS)
PSA progression is defined as a rise in PSA at \> 12 weeks by more than 25% and more than 2ng/mL above the nadir (lowest PSA point). Time-to-event endpoints will be analyzed graphically and numerically using the Kaplan-Meier method and summarized in terms of median or 1-year survival point estimates with corresponding 95% confidence intervals.
Incidence of adverse events (AEs)
AEs will be graded in severity according to the Common Terminology Criteria for Adverse Events version 5.0. Will be analyzed descriptively using summaries of counts and proportions of total and type-specific grade 3/4 AEs across cycles. The maximum toxicity grade per patient of each AE will be derived and presented in table format. The number of patients with grade 3 or higher toxicities (for each toxicity type and overall) will be provided. All AEs will be described, including clinically relevant biochemical and hematological values.
PSA50 response
Will be determined if an average of 70% of patients who receive the intensified regimen achieve a ≥ 50% PSA reduction in favor of the intensified regimen based on a 1-sample test of binomial proportions with 1-sided alpha = 5%. Local labs will measure PSA levels. Increases and decreases will be tracked to assess PSA responses as per Prostate Cancer Working Group 3 (PCWG3). Will be summarized as proportions with 95% confidence intervals calculated using Wilson's method and visualized using waterfall plots.
Radiographic progression-free survival
Time to radiographic progression is defined using conventional imaging or death due to any cause, whichever occurs first. Radiographic progression will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 for soft tissue and PCWG3 for bone lesions. Will analyzed based on a 1-sample test of binomial proportions with 1-sided alpha = 5%. Time-to-event endpoints will be analyzed graphically and numerically using the Kaplan-Meier method and summarized in terms of median or 1-year survival point estimates with corresponding 95% confidence intervals.
Overall response rate (ORR)
ORR is defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) as measured by RECIST v1.1 response in soft tissue, lymph node and visceral lesions. Will analyzed based on a 1-sample test of binomial proportions with 1-sided alpha = 5%.
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University of Washington
Lead sponsor
Novartis
Collaborator
Society of Nuclear Medicine and Molecular Imaging (SNMMI) Mars Shot Research Fund
Collaborator
