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

NCT06943495 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2025-7829
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Can the administered activity (cumulative or per-cycle) be increased in a majority of participants?
2. 2.What is the incidence of some specific adverse reactions during the treatment?

Conditions

Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Outcome Measures

Primary Outcomes (2)

• Administered activity of 177Lu-PSMA-617

  In GBq, cumulative and average per cycle.

  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)

  Subacute AESIs are: * treatment-related grade 3-4 thrombopenia persisting more than 12 weeks * treatment-related grade 3-4 neutropenia persisting more than 12 weeks * treatment-related creatinine elevation to \>2x baseline and \>ULN (upper limit of normal) persisting more than 12 weeks * treatment-related grade 4 febrile neutropenia * treatment-related grade 4 non-hematological toxicity

  From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)

Secondary Outcomes (17)

• Best biochemical response

  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)

  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

  From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)

• Radiological progression-free survival (rPFS)

  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

  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

Study Arms (2)

Personalized activity

EXPERIMENTAL

Drug: 177Lu-PSMA-617

Fixed activity

ACTIVE COMPARATOR

Drug: 177Lu-PSMA-617

Interventions

177Lu-PSMA-617 DRUG

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

Personalized activity

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jean-Mathieu Beauregard: lead
• CHU de Quebec-Universite Laval: collaborator
• Novartis: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

CHU de Québec-Université Laval

Québec, Quebec, G1R2J6, Canada

RECRUITING

MeSH Terms

Interventions

Pluvicto

Study Officials

• Jean-Mathieu Beauregard, MD

  CHU de Québec-Université Laval

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie-Christine Dubé, Ph.D.

CONTACT

418-525-4444; marie-christine.dube@crchudequebec.ulaval.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Nuclear Medicine Physician

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: April 24, 2025
• Study Start: August 15, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2033
• Last Updated: September 9, 2025

Record last verified: 2025-09

Locations

CA (1)