Low PSMA SUV Boost (LPS-Boost): Intensified 177Lu-PSMA-617 Treatment for Patients With Metastatic Castrate-Resistant Prostate Cancer With Low PSMA Expressing Disease
NCT Number: NCT06526299
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Castration-Resistant Prostate Carcinoma|Metastatic Prostate Carcinoma|Stage IVB Prostate Cancer AJCC v8
Interventions: PROCEDURE: Biospecimen Collection|PROCEDURE: Bone Scan|PROCEDURE: Computed Tomography|DRUG: Lutetium Lu 177 Vipivotide Tetraxetan|PROCEDURE: Magnetic Resonance Imaging|PROCEDURE: PSMA PET-CT Scan|OTHER: Questionnaire Administration|PROCEDURE: Single Photon Emission Computed Tomography
Sponsor: University of Washington
Collaborators: Novartis|Society of Nuclear Medicine and Molecular Imaging (SNMMI) Mars Shot Research Fund
Sex: MALE
Age: ADULT, OLDER_ADULT
Enrollment: 51
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-12-01
Completion Date: 2027-12-31
Locations: University of California San Francisco, San Francisco, California, 94143, United States|Olive View-University of California Los Angeles Medical Center, Sylmar, California, 91342, United States|Fred Hutch/University of Washington Cancer Consortium, Seattle, Washington, 98109, United States

Summary:
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.

Primary Outcome Measures: 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)., From enrollment to PSA progression or death from any cause, assessed up to 2 years
Secondary Outcome Measures: Incidence of adverse events (AEs), AEs will be graded in severity according to the Common Terminology Criteria for Adverse Events version 5.0., Up to 30 days post-treatment|PSA responses, 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)., Up to 30 days post-treatment|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%., From enrollment to radiographic disease progression or death from any cause, assessed up to 2 years|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%., Up to 2 years|Duration of response (DOR), DOR will also be measured in patients with a CR or PR from date of first response to the date of RECIST progression or death. Will analyzed based on a 1-sample test of binomial proportions with 1-sided alpha = 5%., Up to 2 years|Progression-free survival (PFS), Clinical progression is defined as the development of signs or symptoms related to prostate cancer as assessed by the physician, initiation of other oncologic treatment or death. Will analyzed based on a 1-sample test of binomial proportions with 1-sided alpha = 5%., From enrolment to first evidence of radiographic or clinical progression, or PSA PFS, assessed up to 2 years|Overall survival, Will analyzed based on a 1-sample test of binomial proportions with 1-sided alpha = 5%., From death from any cause, assessed up to 2 years|Pain score, Pain will be assessed using the Brief Pain Inventory - Short Form to assess the severity of pain and the impact of pain on daily functions. Measured on Scale of 0 to 10, 0 = no pain, 10 = worst pain imaginable. Higher scores reflect more pain severity and more pain interference., Up to 30 days post-treatment|Health-related quality of life: Eastern Cooperative Oncology Group (ECOG) Performance Status scale, Measures one's level of functioning in terms of ability to care for oneself, daily activity, and physical ability (walking, working, etc.) with a range of 0 to 5. A score of 0 indicates performance without restriction whereas a score of 5 indicates death (a higher score indicates worse functioning)., Up to 30 days post-treatment|Health-related quality of life: Functional Assessment of Cancer Therapy Prostate (FACT-P), The FACT-P questionnaire will also be administered to assess the health-related quality of life (HRQoL) of prostate cancer patients. The FACT-P is made up of 2 parts: the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire with 27 questions, and the Prostate Cancer Subscale (PCS) with an additional 12 questions. The FACT-G questionnaire measures HRQoL in four different domains: Physical well-being, Functional well-being, Emotional well-being, and Social/Family well-being. The PCS is designed specifically to measure prostate cancer-specific quality of life.

Each item in both the FACT-G and PCS is rated on a 0 to 4 Likert-type scale, 0 being "not at all" and 4 being "very much", and then combined to produce subscale scores for each domain, as well as global quality of life score, with higher scores representing better quality of life., Up to 30 days post-treatment