Personalized vs. Fixed-Activity 177Lu-PSMA-617 Radiopharmaceutical Therapy (PRODIGY-2)

Official title

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)

Overview

The goal of this clinical trial is to assess if a personalized regime of 177Lu-PSMA-617 (Lutetium Lu 177 vipivotide tetraxetan, also known as Pluvicto) is feasible and safe in a population of patients with metastatic castrate-resistant prostate cancer (mCRPC). The main questions it aims to answer are: 1. Can the administered activity (cumulative or per-cycle) be increased in a majority of participants? 2. What is the incidence of some specific adverse reactions during the treatment? Researchers will compare participants receiving a personalized regime to participants receiving the standard fixed-activity regime of 177Lu-PSMA-617 to see if the activity can be safely increased through personalization based on renal dosimetry (i.e. the measure of how much radiation is actually delivered to the kidney). Participants will receive up to 6 treatments of 177Lu-PSMA-617 every 6 weeks and be regularly evaluated with imaging and laboratory tests, as well as with questionnaires.

Interventions

• Drug 177Lu-PSMA-617
  6 cycles of personalized activity (1st cycle based on BSA and eGFR; cycles 2-6 based on renal dosimetry), maximum 22.2 GBq, every 6 weeks
• Drug 177Lu-PSMA-617
  6 cycles of 7.4 GBq every 6 weeks

Primary outcome measures

• Administered activity of 177Lu-PSMA-617 [Time frame: From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)]
• Number of participants with subacute adverse events of special interest (AESIs) [Time frame: From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)]

Secondary outcome measures (12)

• Best biochemical response [Time frame: From first administration until 52 weeks or the start of another anti-cancer treatment or death, whichever is earliest]
• PSA progression-free survival (PSA-PFS) [Time frame: From date of first administration until the date of PSA progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months]
• Best radiological response rates [Time frame: From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)]
• Radiological progression-free survival (rPFS) [Time frame: From date of first administration until the date of radiological progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months]
• Investigator-assessed overall PFS [Time frame: From date of first administration until the date of investigator-assessed progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months]
• Time to first symptomatic skeletal event (SSE) [Time frame: From date of first administration until the date of first SSE or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months]
• Overall survival (OS) [Time frame: From date of first administration until the date of death, assessed over a minimum of 60 months]
• Metabolic response on FDG-PET/CT [Time frame: At baseline and at 12 weeks]
• Molecular response on PSMA-PET/CT [Time frame: At baseline and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)]
• Best molecular response on quantitative 177Lu SPECT/CT during treatment [Time frame: From first cycle's Day 3 until the last cycle's Day 3 (each cycle is 6 weeks, up to 6 consecutive cycles)]
• Number of participants with any adverse events (AEs) [Time frame: From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)]
• Number of participants with laboratory adverse events (AEs) [Time frame: From date of first administration until the date of investigator-assessed progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months]

Eligibility criteria

Inclusion criteria

• Patient aged ≥18 years with metastatic adenocarcinoma of the prostate, defined by documented histopathology of prostate adenocarcinoma;
• Castration-resistant prostate cancer, as defined as disease progressing despite castration by orchiectomy or ongoing androgen deprivation therapy;
• 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);
• PSA ≥2 ng/mL ;
• Prior treatment with at least one ARPI;
• 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;
• ECOG Performance status 0 to 2;
• Calculated eGFR (by CKD-EPI formula) ≥ 45 mL/min/1.73m\^2;
• Albumin ≥ 25 g/L;
• Platelets ≥ 100x10\^9/L;
• Neutrophils ≥ 1.5x10\^9/L;
• Hemoglobin ≥ 90 g/L without transfusion in the past 4 weeks;
• Signed, written informed consent

Exclusion criteria

• PSMA-PET "superscan" (i.e. extensive/diffuse PSMA-positive bone involvement);
• 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;
• 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);
• Prior radiopharmaceutical therapy;
• 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;
• Active malignancy other than prostate cancer;
• Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception;
• Any other condition, diagnosis or finding that may in the investigator's opinion interfere with trial conduct;
• Known hypersensitivity to 177Lu-PSMA-617 or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• CHU de Québec-Université Laval — Québec

Identifiers

NCT: NCT06943495 · 2025-7829

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗