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NCT Number: NCT06943495

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

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.

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Key information

Conditions

Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

CHU de Québec-Université Laval

Québec, Quebec, G1R2J6, Canada

Location status: Recruiting

Location contact

Jean-Mathieu Beauregard, MD

PRINCIPAL_INVESTIGATOR

Marie-Christine Dubé, Ph.D.

CONTACT

[email protected]

418-525-4444

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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

Primary outcomes

  1. 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)

    In GBq, cumulative and average per cycle.

  2. 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)

    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

Secondary outcomes

  1. Best biochemical response

    Time frame: From first administration until 52 weeks or the start of another anti-cancer treatment or death, whichever is earliest

    Maximum percent decrease of serum prostate-specific antigen (PSA) after first administration.

  2. 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

    Time from first administration to an increase in PSA greater than 25%, and greater than 2 ng/ml, above nadir, confirmed at least 3 weeks later.

  3. Best radiological response rates

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

    Percentage of participants achieving each RECIST 1.1 response category as their best response: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), overall response (i.e., CR or PR; a.k.a. overall response rate, ORR), disease control (i.e CR, PR or SD; a.k.a. disease control rate, DCR).

  4. 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

    Time from first administration to the date of radiographic disease progression based on RECIST 1.1/PCWG3.

  5. 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 from first administration to the earliest of clinical (worsening of a patient's clinical status attributed to disease progression), biochemical or radiological progression considering all data (scheduled and unscheduled) available to the investigator.

  6. 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

    Time to first Symptomatic Skeletal Event (SSE) is defined as the time from first administration to the date of the SSE. The SSE date is the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever occurred first.

  7. Overall survival (OS)

    Time frame: From date of first administration until the date of death, assessed over a minimum of 60 months

    Overall Survival (OS) is defined as the time from the date of the first administration to the date of death due to any cause.

  8. Metabolic response on FDG-PET/CT

    Time frame: At baseline and at 12 weeks

    Metabolic response is defined as complete metabolic response (CMR, disappearance of all lesions on FDG PET), partial metabolic response (PMR, decrease of uptake by ≥30%), stable metabolic disease (SMD, variation of FDG uptake by <30%), progressive metabolic disease (PMD, increase of FDG uptake by ≥30%)

  9. 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)

    Molecular response is defined as the variation of molecular tumor volume (MTV) on PSMA-PET/CT

  10. 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)

    Best molecular response is defined as the maximum percent decrease of molecular tumor volume (MTV) at any time after post-treatment quantitative 177Lu SPECT/CT performed on the first cycle's Day 3, up to the post-treatment quantitative 177Lu SPECT/CT performed on the last cycle's Day 3

  11. 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)

    All adverse events that occur from the first administration of 177Lu-PSMA-617 until 6 weeks after the last administration of 177Lu-PSMA-617 or prior to the initiation of subsequent anticancer treatment.

  12. 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

    Adverse events seen on laboratory (hematology, biochemistry) that occur from the first administration of 177Lu-PSMA-617 until progression or until the initiation of subsequent anticancer treatment if earlier.

  13. Number of participants with delayed adverse events of special interest (AESIs)

    Time frame: From date of first administration until the date of death, assessed over a minimum of 60 months

    Delayed AESIs (renal impairment and secondary hematological malignancies) that occur from the first administration of 177Lu-PSMA-617 until death (or study termination)

  14. Variation of score on EuroQol-5 Dimension-5 Level (EQ-5D-5L) questionnaire at baseline

    Time frame: At baseline, at 18 weeks, and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)

  15. Variation of score on Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire at baseline

    Time frame: At baseline, at 18 weeks, and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)

  16. Variation of score on Brief Pain Inventory (BPI-SF) questionnaire at baseline

    Time frame: At baseline, at 18 weeks, and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)

  17. Variation of score on Multidisciplinary Salivary Gland Society (MSGS) questionnaire at baseline

    Time frame: At baseline, at 18 weeks, and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)

Study contacts

Contact information is provided by the study sponsor or research team.

Marie-Christine Dubé, Ph.D.

CONTACT

[email protected]

418-525-4444

Sponsors and collaborators

Lead sponsor

Jean-Mathieu Beauregard

Other

Collaborators

  • CHU de Quebec-Universite Laval
  • Canadian Institutes of Health Research (CIHR)
  • Novartis

Registry information

Official study 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)

Acronym: PRODIGY-2

Important dates

Study start
2025
Primary completion
2029
Study completion
2033
First posted
Apr 24, 2025
Registry last updated
Sep 9, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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