Personalized versus fixed‑dose Lutetium‑177 PSMA therapy for metastatic castration‑resistant prostate cancer

PROstate-specific Membrane Antigen DosImetry- Guided endoradiotherapY: A Randomized- Controlled, Single-blind, Pilot Study of Personalized vs. Fixed-activity 177Lu-PSMA-617 Radiopharmaceutical Therapy (PRODIGY-2)

This study will test whether personalizing Lutetium‑177 PSMA dosing using kidney dosimetry lets men with metastatic castration‑resistant prostate cancer safely receive higher treatment activity than the standard fixed dosing.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: CHU de Quebec-Universite Laval (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Québec, Quebec)
• Trial ID: NCT06943495 on ClinicalTrials.gov

What this trial studies

Participants with PSMA‑positive metastatic castration‑resistant prostate cancer are randomized to receive either a standard fixed activity or a personalized activity of Lutetium‑177‑PSMA‑617 guided by renal dosimetry. Up to six treatment cycles are given every six weeks, with regular imaging, laboratory tests, and patient questionnaires to track safety and exposure. The trial specifically aims to see whether cumulative or per‑cycle activity can be increased in most participants under the personalized approach and to document the incidence of predefined adverse reactions. This is a Phase 1, single‑center safety and feasibility study conducted at an academic hospital.

Who should consider this trial

Good fit: Men with PSMA‑positive metastatic castration‑resistant prostate cancer who have progressed after at least one androgen receptor pathway inhibitor, have ECOG performance status 0–2, adequate blood counts and albumin, and estimated GFR ≥45 mL/min/1.73 m² are the intended candidates.

Not a fit: Patients with low or absent PSMA expression on PET, poor kidney function, inadequate blood counts or albumin, or who cannot travel to the study center are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, personalization could allow higher effective radiation doses to tumors while keeping kidney exposure within safe limits, potentially improving cancer control.

How similar studies have performed: Large randomized trials have shown benefit of fixed‑activity 177Lu‑PSMA‑617, while renal dosimetry–guided dose escalation has been explored in smaller studies and remains investigational.

Eligibility criteria

Inclusion Criteria:

1. Patient aged ≥18 years with metastatic adenocarcinoma of the prostate, defined by documented histopathology of prostate adenocarcinoma;
2. Castration-resistant prostate cancer, as defined as disease progressing despite castration by orchiectomy or ongoing androgen deprivation therapy;
3. Progressive mCRPC with rising PSA level, defined by PCWG3 criteria (sequence of two rising values above a baseline at a minimum of 1-week intervals, with serum testosterone level ≤ 1.7 nmol/dL);
4. PSA ≥2 ng/mL ;
5. Prior treatment with at least one ARPI;
6. PSMA-expressing cancer, with significant PSMA expression defined as SUVpeak in at least one lesion that is superior to SUVmean of the liver on PSMA-PET (68Ga-PSMA-11 or 18F-DCFPyL), within 45 days prior to randomization;
7. ECOG Performance status 0 to 2;
8. Calculated eGFR (by CKD-EPI formula) ≥ 45 mL/min/1.73m\^2;
9. Albumin ≥ 25 g/L;
10. Platelets ≥ 100x10\^9/L;
11. Neutrophils ≥ 1.5x10\^9/L;
12. Hemoglobin ≥ 90 g/L without transfusion in the past 4 weeks;
13. Signed, written informed consent

Exclusion Criteria:

1. PSMA-PET "superscan" (i.e. extensive/diffuse PSMA-positive bone involvement);
2. Site(s) of disease that are FDG-positive, defined as SUVpeak in at least one lesion that is superior to twice (2x) SUVmean of the liver, and PSMA-negative (as above), within 45 days prior to randomization;
3. Prior treatment with more than two lines of chemotherapy for mHSPC and/or mCRPC (adjuvant and neoadjuvant chemotherapy does not count) towards the maximum of two regimens);
4. Prior radiopharmaceutical therapy;
5. Known CNS metastasis unless they are deemed to be non-progressive, asymptomatic and off corticosteroid therapy for at least four weeks, as per investigator's assessment;
6. Active malignancy other than prostate cancer;
7. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception;
8. Any other condition, diagnosis or finding that may in the investigator's opinion interfere with trial conduct;
9. Known hypersensitivity to 177Lu-PSMA-617 or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

Where this trial is running

Québec, Quebec

• CHU de Québec-Université Laval — Québec, Quebec, Canada (Recruiting)

Study contacts

• Principal investigator: Jean-Mathieu Beauregard, MD — CHU de Québec-Université Laval
• Study coordinator: Marie-Christine Dubé, Ph.D.

Conditions Metastatic Castrate Resistant Prostate Cancer