Clinical trial NCT05896371: A Phase 1/2 Study of Personalized PSMA Radiopharmaceutical Therapy
Official title: PROstate-specific Membrane Antigen DosImetry-Guided EndoradiotherapY: a Phase 1/2 Study of Personalized PSMA Radiopharmaceutical Therapy (PRODIGY-1)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cancer
Prostate Cancer
Metastatic Cancer
Metastatic Prostate Cancer
Keywords: Prostate-Specific Membrane Antigen
177Lu-PSMA
Radiopharmaceutical Therapy
Dosimetry
Personalized
Lead sponsor: CHU de Quebec-Universite Laval
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2023-06-09
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to study a personalized regime of lutetium-177 (177Lu) prostate-specific membrane antigen (PSMA) radiopharmaceutical therapy (RPT) in patients with progressive and/or symptomatic, inoperable PSMA-expressing cancers of prostatic or other origins.

The main questions it aims to answer are:

* To establish a dosimetry-based, personalized regime of 177Lu-PSMA
* To report on the efficacy of personalized 177Lu-PSMA

Participants (stratified by risk factors of toxicity) will receive up to 6 cycles of a personalized activity of 177Lu-PSMA based on renal dosimetry. In the phase 1, the prescribed absorbed dose to the kidney will be escalated, to determine the regime that will be administered in the phase 2. The best response within 12 months after the first cycle will be assessed. Salvage treatment of 3 cycles may be offered to responders after re-progression.


Eligibility criteria: Inclusion Criteria:

* \>18 y.o. adults able to provide consent
* Inoperable or metastatic PSMA-expressing cancer, with significant PSMA expression defined as uptake in at least one lesion that is superior to that of the liver on PSMA positron-emission tomography (PET) within 3 months prior to enrolment
* Cancer progression documented within 3 months prior to enrolment as per the investigator's assessment, without initiation of another anti-cancer treatment since (excluding palliative radiation therapy to a minority of the tumor burden), unless that anti-cancer treatment was stopped prematurely because of intolerance
* For participants with a cancer other than mCRPC, a recommendation from a multidisciplinary tumor board (MDT) in favor of PSMA RPT must be obtained

Exclusion Criteria:

* Platelets \< 50 x 106/L
* Absolute neutrophil count (ANC) \< 1.0 x 106/L
* Eastern Cooperative Oncology Group (ECOG) 4 or prognosis \< 3 months, for cancer-related or other serious medical conditions, as per investigator's assessment
* Known presence of central nervous system metastasis at risk of complication, which cannot be adequately stabilized (e.g. radiotherapy or corticoid prophylaxis), as per investigator's assessment
* Any condition that would limit the ability to comply with the study protocol, as per investigator's assessment
* Pregnancy or breastfeeding (e.g. for female participants with non-prostate cancer)

Primary outcomes:
measure: Phase 1: Number of dose-limiting toxicities (DLTs)
timeFrame: 12 weeks
measure: Phase 2: Overall response rate (ORR)
timeFrame: Up to 12 months
measure: Phase 2: Biochemical response rate (PSA50)
timeFrame: Up to 12 months
Secondary outcomes:
measure: Frequency and grades of treatment-related adverse events (AEs)
timeFrame: Up to 12 months
measure: Delayed AEs of particular interest
timeFrame: Up to 5 years
measure: Phase 1: Overall response rate (ORR)
timeFrame: Up to 12 months
measure: Phase 1: Biochemical response rate (PSA50)
timeFrame: Up to 12 months
measure: Quality of life patient-reported outcome measures (PROMs) response rates
timeFrame: Up to 12 months
measure: Progression-free survival (PFS)
timeFrame: Up to 5 years
measure: Overall survival (OS)
timeFrame: Up to 5 years
Other outcomes:
Locations:
Study officials:
affiliation: CHU de Québec - Université Laval
name: Jean-Mathieu Beauregard, MD,MSc,FRCPC
role: PRINCIPAL_INVESTIGATOR
References: