A Phase 1/2 Study of Personalized PSMA Radiopharmaceutical Therapy

Study Overview
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Brief Summary
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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.

Official Title
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PROstate-specific Membrane Antigen DosImetry-Guided endoradiotherapY: A Phase 1/2 Study of Personalized PSMA Radiopharmaceutical Therapy (PRODIGY-1)

Conditions
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Cancer, Prostate Cancer, Metastatic Cancer, Metastatic Prostate Cancer

Intervention / Treatment
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* Drug: 177Lu-PSMA-I&T - escalating renal absorbed dose
* Drug: 177Lu-PSMA-I&T - recommended phase 2 regime


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Lower risk of toxicity (no risk factor) | Drug: 177Lu-PSMA-I&T - escalating renal absorbed dose<br>* Personalized 177Lu-PSMA-I&T injected activity<br>Drug: 177Lu-PSMA-I&T - recommended phase 2 regime<br>* Personalized 177Lu-PSMA-I&T injected activity<br>|
| Experimental: Cohort B<br>Extensive bone metastasis | Drug: 177Lu-PSMA-I&T - escalating renal absorbed dose<br>* Personalized 177Lu-PSMA-I&T injected activity<br>Drug: 177Lu-PSMA-I&T - recommended phase 2 regime<br>* Personalized 177Lu-PSMA-I&T injected activity<br>|
| Experimental: Cohort C<br>Decreased bone marrow reserve | Drug: 177Lu-PSMA-I&T - escalating renal absorbed dose<br>* Personalized 177Lu-PSMA-I&T injected activity<br>Drug: 177Lu-PSMA-I&T - recommended phase 2 regime<br>* Personalized 177Lu-PSMA-I&T injected activity<br>|
| Experimental: Cohort D<br>Renal function impairment | Drug: 177Lu-PSMA-I&T - escalating renal absorbed dose<br>* Personalized 177Lu-PSMA-I&T injected activity<br>Drug: 177Lu-PSMA-I&T - recommended phase 2 regime<br>* Personalized 177Lu-PSMA-I&T injected activity<br>|
| Experimental: Cohort E<br>Higher risk of toxicity (more than one risk factor and others) | Drug: 177Lu-PSMA-I&T - escalating renal absorbed dose<br>* Personalized 177Lu-PSMA-I&T injected activity<br>Drug: 177Lu-PSMA-I&T - recommended phase 2 regime<br>* Personalized 177Lu-PSMA-I&T injected activity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Number of dose-limiting toxicities (DLTs) |  | 12 weeks | 
| Phase 2: Overall response rate (ORR) |  | Up to 12 months | 
| Phase 2: Biochemical response rate (PSA50) |  | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and grades of treatment-related adverse events (AEs) |  | Up to 12 months | 
| Delayed AEs of particular interest |  | Up to 5 years | 
| Phase 1: Overall response rate (ORR) |  | Up to 12 months | 
| Phase 1: Biochemical response rate (PSA50) |  | Up to 12 months | 
| Quality of life patient-reported outcome measures (PROMs) response rates |  | Up to 12 months | 
| Progression-free survival (PFS) |  | Up to 5 years | 
| Overall survival (OS) |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate-Specific Membrane Antigen, 177Lu-PSMA, Radiopharmaceutical Therapy, Dosimetry, Personalized