A Phase 1/2 Study of Personalized PSMA Radiopharmaceutical Therapy

Phase 1

Not yet recruiting

• Conditions: Cancer; Prostate Cancer; Metastatic Cancer; Metastatic Prostate Cancer
• Interventions: Drug: 177Lu-PSMA-I&T - escalating renal absorbed dose; Drug: 177Lu-PSMA-I&T - recommended phase 2 regime

• Registration Number: NCT05896371
• Lead Sponsor: CHU de Quebec-Universite Laval

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-31
• Study First Submitted QC: 2023-05-31
• Study First Posted: 2023-06-09
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30
• Study Start: 2028-03
• Primary Completion: 2033-03
• Study Completion: 2034-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 500

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort A	177Lu-PSMA-I&T - recommended phase 2 regime	Lower risk of toxicity (no risk factor)
Cohort B	177Lu-PSMA-I&T - escalating renal absorbed dose	Extensive bone metastasis
Cohort B	177Lu-PSMA-I&T - recommended phase 2 regime	Extensive bone metastasis
Cohort C	177Lu-PSMA-I&T - escalating renal absorbed dose	Decreased bone marrow reserve
Cohort A	177Lu-PSMA-I&T - escalating renal absorbed dose	Lower risk of toxicity (no risk factor)
Cohort C	177Lu-PSMA-I&T - recommended phase 2 regime	Decreased bone marrow reserve
Cohort D	177Lu-PSMA-I&T - escalating renal absorbed dose	Renal function impairment
Cohort D	177Lu-PSMA-I&T - recommended phase 2 regime	Renal function impairment
Cohort E	177Lu-PSMA-I&T - escalating renal absorbed dose	Higher risk of toxicity (more than one risk factor and others)
Cohort E	177Lu-PSMA-I&T - recommended phase 2 regime	Higher risk of toxicity (more than one risk factor and others)

Primary Outcome Measures

Name	Time	Method
Phase 2: Overall response rate (ORR)	Up to 12 months
Phase 1: Number of dose-limiting toxicities (DLTs)	12 weeks
Phase 2: Biochemical response rate (PSA50)	Up to 12 months

Secondary Outcome Measures

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