NCT07054346 · Thomas Hope
Comparison of 177Lu-PSMA-617 and 225Ac-PSMA-617
(LUTACT)
What this study is about
There is evidence that Actinium-225 Prostate-Specific Membrane Antigen (225Ac-PSMA) has a potentially higher level of effectiveness than 177 Lutetium Prostate-Specific Membrane Antigen (177Lu-PSMA) as a radioligand therapy.
View original scientific description
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.
Interventions
DRUG
177 Lutetium Prostate-Specific Membrane Antigen 617
Given intravenously (IV) or intra-arterially (IA)
DRUG
Actinium-225 Prostate-Specific Membrane Antigen 617
Given IV or IA
PROCEDURE
Non-investigational, Prostatectomy
Undergo non-investigational surgical procedure to remove prostate.
PROCEDURE
Prostate Tissue Collection
Whole prostate tissue will be collected for correlative research at time of prostatectomy.
PROCEDURE
Single-photon emission computed tomography (SPECT)/Computerized tomography (CT)
Imaging procedure
PROCEDURE
Blood Sample Collection
Blood samples will be obtained for research purposes
Primary outcome measures
Mean of tumor absorbed dose (Cohorts 1 and 2)
Time frame: 1 week
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.
Rate of Cluster of differentiation 3 positive (CD3+) T cell infiltration
Time frame: 1 day, at time of prostatectomy
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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).
- Creatinine clearance Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 , calculated using the Cockcroft-Gault equation.
- Albumin ≥2.5 g/dL.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN.
- Total bilirubin (TBIL) ≤2 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3 x ULN is permitted.
- Ability to understand and the willingness to sign a written informed consent document.
- Participants must provide consent to comply to recommended radioprotection precautions during study.
- Participants must use adequate contraception and not donate sperm while on study drug and for at least 14 weeks after the last study treatment.
Exclusion criteria
- 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. Additional exclusion criteria applicable only to participants undergoing intraarterial administration of PSMA RLT:
- 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.
Where
- San Francisco, California
Collaborators
Novartis
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 1, 2026 · Source of record for eligibility and locations