Personalized vs. Fixed-Activity 177Lu-PSMA-617 Radiopharmaceutical Therapy (PRODIGY-2)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexMale
Age18+
SponsorJean-Mathieu Beauregard
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 ;
Disqualifiers
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;
Trial design
Design model
Parallel
Treatments tested in this trial
177Lu-PSMA-617
Drug6 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
177Lu-PSMA-617
Drug6 cycles of 7.4 GBq every 6 weeks
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Personalized activityExperimental treatment 1 intervention
Group B: Fixed activityActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Administered activity of 177Lu-PSMA-617
In GBq, cumulative and average per cycle.
Time frame
From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)2
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
Time frame
From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)Secondary outcomes
1
Best biochemical response
Maximum percent decrease of serum prostate-specific antigen (PSA) after first administration.
Time frame
From first administration until 52 weeks or the start of another anti-cancer treatment or death, whichever is earliest2
PSA progression-free survival (PSA-PFS)
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.
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 months3
Best radiological response rates
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).
Time frame
From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)4
Radiological progression-free survival (rPFS)
Time from first administration to the date of radiographic disease progression based on RECIST 1.1/PCWG3.
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 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Jean-Mathieu Beauregard
Lead sponsor
CHU de Quebec-Universite Laval
Sponsor institution
CHU de Quebec-Universite Laval
Collaborator
Novartis
Collaborator
Canadian Institutes of Health Research (CIHR)
Collaborator
Source ClinicalTrials.gov