Comparison of 177Lu-PSMA-617 and 225Ac-PSMA-617
LUTACT
2 other identifiers
interventional
45
1 country
1
Brief Summary
There is evidence that Actinium-225 Prostate-Specific Membrane Antigen (225Ac-PSMA) has a potentially higher level of efficacy than 177 Lutetium Prostate-Specific Membrane Antigen (177Lu-PSMA) as a radioligand therapy. This single center, pilot study will compare differences in the mechanisms of actinium-225 and lutetium-177 radioligand therapies (RLT) in participants with high or very high risk localized or locoregional prostate cancer planning on undergoing a prostatectomy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 prostate-cancer
Started Jul 2025
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 28, 2025
CompletedFirst Posted
Study publicly available on registry
July 8, 2025
CompletedStudy Start
First participant enrolled
July 8, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2028
April 1, 2026
March 1, 2026
1.8 years
June 28, 2025
March 26, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Mean of tumor absorbed dose (Cohorts 1 and 2)
The mean tumor absorbed dose on post-treatment SPECT imaging within 7 days of the first radioligand treatment (RLT) will be obtained by using MIM Software to measure absorbed dose and researchers will manually segment activity in the dominant prostate tumor while carefully excluding any activity within the bladder using a threshold of 5 Gray. Using this segmented volume, the mean dose within the tumor in Gray for each participant and standard deviation will be calculated and reported descriptively for Cohorts 1 and 2. A two-sample t-test comparing the dose between Cohort 1 and Cohort 2 and Analysis of Variance (ANOVA) model to compare the dose between different treatment/fractionation modalities within each cohort will be performed.
1 week
Rate of Cluster of differentiation 3 positive (CD3+) T cell infiltration
Immunohistochemistry will be performed using standard methods, and stained slides will be scanned using an automated microscope scanner. Five randomly selected fields (0.25 mm\^2) from each participant's primary tumor will be captured. Using color-specific algorithms, CD3+ cell counts will be determined, and the mean of each of the five quantified fields will be used. We will use a two-sample t-test or ANOVA model comparing the CD3+ cell counts between Cohort 1 and Cohort 2 with participants who have not undergone prostatectomy enrolled in the biospecimen protocol, respectively.
1 day, at time of prostatectomy
Secondary Outcomes (5)
Proportion of participants with reported treatment-emergent adverse events (Cohorts 1 and 2)
Up to 6 weeks after last PSMA RLT administration
Proportion of participants with perioperative complications
Up to 6 weeks after prostatectomy
Median scores on the xerostomia-quality-of-life-scale (XeQoLS)
Up to 12 months after prostatectomy
Proportion of participants with 50% decrease in level of prostate specific antigen (PSA50)
Up to 8 weeks
Proportion of participants with complete pathologic response
1 day, at time of prostatectomy
Study Arms (3)
Cohort 1 (177Lu-PSMA-617)
EXPERIMENTALFive participants will receive a single dose of 177Lu-PSMA-617 radioligand therapy intravenously (IV), five participants will receive a single dose of 177Lu-PSMA-617 intra-arterially (IA), and five participants will receive two doses over 6 weeks intravenously. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
Cohort 2 (225Ac-PSMA-617)
EXPERIMENTALFive participants will receive a single dose of 225Ac-PSMA-617 radioligand therapy IV, five participants will receive a single dose of 225Ac-PSMA-617 IA, and five participants will receive two doses over 6 weeks IV. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
Control Group (Prostatectomy only)
OTHERParticipants will obtain a non-investigational prostatectomy. Tumor tissue obtained at the time of surgery will be utilized for comparisons with the cohorts receiving study therapies. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and up to 24 months after surgery.
Interventions
Given IV or IA
Undergo non-investigational surgical procedure to remove prostate.
Whole prostate tissue will be collected for correlative research at time of prostatectomy.
Blood samples will be obtained for research purposes
Given intravenously (IV) or intra-arterially (IA)
Imaging procedure
Eligibility Criteria
You may qualify if:
- Histologically confirmed prostate adenocarcinoma.
- Willing to undergo prostatectomy with or without lymph node dissection, and candidate for prostatectomy as determined by urologic oncology.
- High-risk disease as defined as meeting 1 or more of the 3 following criteria:
- Gleason score of 4+5 disease or higher.
- Pelvic nodal metastases on PSMA PET.
- Extracapsular extension or seminal vesicle invasion on MRI.
- No evidence of distant metastatic disease as determined by PSMA PET. Nodal disease below the iliac bifurcation (clinical stage N1) is allowed.
- Maximum Standardized Uptake Value (SUVmax) in the primary tumor greater than 10 on PSMA PET using Gallium-68 (68Ga)-PSMA-11 or piflufolastat F 18 (18F-DCFPyL).
- Target tumor in the prostate measuring greater than 1.5 cm on MRI.
- Age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%),
- Demonstrates adequate organ function as defined below:
- Platelets ≥100,000/mcL, independent of transfusions or growth factors within 3 months of treatment start.
- Hemoglobin ≥10 g/dL, independent of transfusions or growth factors within 3 months of treatment start.
- Absolute Neutrophil Count (ANC) ≥1,500/microliter (mcL).
- +7 more criteria
You may not qualify if:
- Has received prior prostate cancer therapy.
- a. Prior 5-alpha reductase inhibitors (e.g. finasteride, dutasteride) allowed if discontinued at least 3 weeks prior to treatment start.
- Has participated in a study of an investigational therapeutic product and received study treatment or used an investigational device within four weeks of the first dose of treatment.
- Dry mouth that impacts the eating of food (i. e. requiring mouthwash prior to eating).
- 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, known active hepatitis B or C or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
- Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free, treatment free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible.
- Individuals with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
- Prior external beam radiation therapy (EBRT) to the prostate or prostate bed.
- Severe allergy to iodinated contrast.
- Severe atherosclerosis from prior CT imaging study, or greater than 10 pack-year smoking history if no prior imaging available.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Thomas Hopelead
- Novartiscollaborator
Study Sites (1)
University of California, San Francisco
San Francisco, California, 94143, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Thomas A Hope, MD
University of California, San Francisco
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor In Residence
Study Record Dates
First Submitted
June 28, 2025
First Posted
July 8, 2025
Study Start
July 8, 2025
Primary Completion (Estimated)
April 30, 2027
Study Completion (Estimated)
April 30, 2028
Last Updated
April 1, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
De-identified data may be shared with study collaborators during the course of the study.