Low PSMA SUV Boost (LPS-Boost): Intensified 177Lu-PSMA-617 Treatment for Patients With Metastatic Castrate-Resistant Prostate Cancer With Low PSMA Expressing Disease
A Phase 2 Study of Biomarker-Modulated PSMA Theranostics
3 other identifiers
interventional
51
1 country
3
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Apr 2025
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 19, 2024
CompletedFirst Posted
Study publicly available on registry
July 29, 2024
CompletedStudy Start
First participant enrolled
April 29, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
March 24, 2026
March 1, 2026
2.7 years
July 19, 2024
March 23, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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.
From enrollment to PSA progression or death from any cause, assessed up to 2 years
Secondary Outcomes (11)
Incidence of adverse events (AEs)
Up to 30 days post-treatment
PSA50 response
Up to 30 days post-treatment
Radiographic progression-free survival
From enrollment to radiographic disease progression or death from any cause, assessed up to 2 years
Overall response rate (ORR)
Up to 2 years
Duration of response (DOR)
Up to 2 years
- +6 more secondary outcomes
Study Arms (1)
Treatment (177Lu-PSMA-617)
EXPERIMENTALPatients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.
Interventions
Undergo blood sample collection
Undergo SPECT/CT and CT
Given IV
Undergo MRI
Undergo PSMA PET/CT
Undergo SPECT/CT
Eligibility Criteria
You may qualify if:
- 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.
- Patients must have a life expectancy \> 6 months.
- Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.
- Patients must have a positive 68Ga-PSMA PET/CT scan with no PSMA negative lesion, as determined by the Nuclear Medicine site investigator. The presence of PSMA-positive lesions was defined as 68Ga-PSMA-11 uptake greater than that of liver parenchyma in one or more metastatic lesions of any size in any organ system. PSMA negative disease defined as lymph nodes of 2.5 cm or visceral lesions or soft tissue component of a lytic bone lesion of 1.0 cm or larger with uptake less than that of liver parenchyma.
- Patients must have whole body tumor SUVmean of \< 10 on 68Ga-PSMA PET/CT scan, as determined by the Nuclear Medicine site investigator. 68GaPSMA PET/CT will be analyzed using a semi-quantitative approach with MIM software (MIM Software Inc.). The workflow identified whole-body regions of interest (ROIs) with an maximum standardized uptake value (SUVmax) greater than 3 and a lesion size of at least 0.5 mm. The reviewer then manually removes any instances of physiological activity or uptake that are not related to the disease. The method of whole-body quantification will automatically calculate the whole body SUVmean.
- Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L) at the most recent evaluation before enrollment.
- Patients must have received at least one androgen receptor pathway inhibitor (ARPI) (such as enzalutamide and/or abiraterone).
- Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:
- Serum 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.
- Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions.
- Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 Prostate Cancer Working Group 3 (PCWG3) criteria, Scher et al 2016).
- Patients must have ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging obtained ≤ 45 days prior to beginning study therapy. Measurable disease by per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 is not required, as prostate cancer patients may not have RECIST-measurable disease but have detectable disease on bone scan.
- +11 more criteria
You may not qualify if:
- 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.
- Known hypersensitivity to the components of the study therapy or its analogs.
- Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
- Transfusion within 30 days of treatment day 1.
- Patients with a history of central nervous system (CNS) metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired.
- Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
- Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
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
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Amir Iravani, MD FRACP
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 19, 2024
First Posted
July 29, 2024
Study Start
April 29, 2025
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
March 24, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share