Comparison of 177Lu-PSMA-617 and 225Ac-PSMA-617

Launched by THOMAS HOPE · Jun 28, 2025

Keywords

ClinConnect Summary

This clinical trial is exploring two different types of targeted radiation treatments for men with high-risk prostate cancer that has not spread to distant parts of the body. The study compares how well a newer therapy using Actinium-225 (called 225Ac-PSMA) works compared to a more established treatment using Lutetium-177 (177Lu-PSMA). Both treatments deliver radiation directly to prostate cancer cells, and this trial aims to understand the differences between them before surgery to remove the prostate (called prostatectomy).

Men who may be eligible for this study are those diagnosed with aggressive prostate cancer based on specific tests, such as biopsy results and imaging scans, showing that the cancer is likely confined to the prostate or nearby lymph nodes but hasn’t spread further. Participants must be planning to have surgery to remove their prostate and meet certain health requirements like good blood counts and kidney and liver function. During the trial, participants will receive one of the two radiation treatments before their surgery, and they will need to follow safety precautions related to radiation. This study is still in early stages and is not yet recruiting participants.

Gender

MALE

Eligibility criteria

• Inclusion Criteria:
• • 1. Histologically confirmed prostate adenocarcinoma.
• • 2. Willing to undergo prostatectomy with or without lymph node dissection, and candidate for prostatectomy as determined by urologic oncology.
• 3. High-risk disease as defined as meeting 1 or more of the 3 following criteria:
• • 1. Gleason score of 4+5 disease or higher.
• • 2. Pelvic nodal metastases on PSMA PET.
• • 3. Extracapsular extension or seminal vesicle invasion on MRI.
• • 4. No evidence of distant metastatic disease as determined by PSMA PET. Nodal disease below the iliac bifurcation (clinical stage N1) is allowed.
• • 5. 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).
• • 6. Target tumor in the prostate measuring greater than 2 cm on MRI.
• • 7. Age ≥18 years.
• • 8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%),
• 9. Demonstrates adequate organ function as defined below:
• • 1. Platelets ≥100,000/mcL, independent of transfusions or growth factors within 3 months of treatment start.
• • 2. Hemoglobin ≥10 g/dL, independent of transfusions or growth factors within 3 months of treatment start.
• • 3. Absolute Neutrophil Count (ANC) ≥1,500/microliter (mcL).
• • 4. Creatinine clearance Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 , calculated using the Cockcroft-Gault equation.
• • 5. Albumin ≥2.5 g/dL.
• • 6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN.
• • 7. Total bilirubin (TBIL) ≤2 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3 x ULN is permitted.
• • 10. Ability to understand and the willingness to sign a written informed consent document.
• • 11. Participants must provide consent to comply to recommended radioprotection precautions during study.
• • 12. 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:
• • 1. 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.
• • 2. 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.
• • 3. Dry mouth that impacts the eating of food (i. e. requiring mouthwash prior to eating).
• • 4. 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.
• • 5. 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.
• • 6. 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.
• Additional exclusion criteria applicable only to participants undergoing intraarterial administration of PSMA RLT:
• • 1. Severe allergy to iodinated contrast.
• • 2. Severe atherosclerosis from prior CT imaging study, or greater than 10 pack-year smoking history if no prior imaging available.