Phase I/II Study Evaluating PSMA Targeted Radionuclide Therapy in Adult Patients With Metastatic Clear Cell Renal Cancer — PRadR  

Metastatic Clear Cell Renal Cell Carcinoma Clinical Trial

Official title: A Multicentric, Single Arm, Open-label, Phase I/II Study Evaluating PSMA Targeted Radionuclide Therapy in Adult Patients With Metastatic Clear Cell Renal Cancer

Status Recruiting

Clinical Trial Summary

This study is an open label Phase I/II study conducted according to a Fleming design, investigating the safety and the efficacy of 4 IV injections of 177Lu-PSMA-1 in patients with metastatic clear cell renal cancer.

This trial is divided in 2 parts:

• A safety run-in part aiming to assess the safety of 177Lu-PSMA-1 (with 6 patients treated at the starting activity = 7.4 GBq of 177Lu-PSMA-1, every 6 weeks (Q6W) for 4 administrations). If more than one patient experiences a ST during the first cycle of therapy (6 weeks), then a lower activity of 177Lu-PSMA-1 will be evaluated in an additional cohort of 6 patients (5.9 GBq). The 6 patients from this safety run-in step, treated at the activity selected for phase II, will be included in the evaluation of Phase II part.

• A Phase II part aiming to assess the clinical activity of 177Lu-PSMA-1

Clinical Trial Description

Despite the improvement in the management of metastatic clear-cell renal cell carcinoma (mccRCC) with antiangiogenic agent and immunotherapy, there is still an unmet need for patients who progress under these therapies. Indeed, there is currently no standard treatment for patients beyond the 2nd line of treatment in the advanced/metastatic setting. Prostate Specific Membrane Antigen (PSMA) is highly expressed in neovessels of various solid tumors including RCC: 86% of ccRCC.Higher grade and stage, metastatic and lethal ccRCC showed higher PSMA expression in tumor vessels, reflecting tumor prognosis. PSMA may be a target expressed in metastatic ccRCC for radionuclide therapy using PSMA Ligands Radiolabeled with Lutetium-177 (PRLT). 177Lu-PSMA delivers ß-particle radiation to PSMA-expressing cells and the surrounding microenvironment with demonstrated efficacy in metastatic prostate cancer. In multitreated prostate cancer patients, the additional effect of 177Lu-PSMA-617 compared to best standard of care alone led to a 4-month OS benefit, with an estimated 38% reduction in risk of death in the 177Lu-PSMA-617 arm compared to the best standard of care arm (median OS 15.3 months versus 11.3 months respectively, hazard ratio [HR]: 0.62, p<0.001).

A phase I/II study will be conducted to evaluate the tolerability and efficacy of 177Lu-PSMA-1 in patients presenting with a PSMA-positive mccRCC selected through 68Ga-PSMA PET. Only patients with tumor tracer uptake greater than background will be treated with 4 cycles of 7.4 GBq of 177Lu-PSMA-1 every 6 weeks.

This study is an open label Phase I/II study conducted according to a Fleming design, investigating the safety and the efficacy of 177Lu-PSMA-1 repeated cycles in patients with metastatic ccRCC.

The study is divided in 2 parts:

• A safety run-in part aiming to assess the safety of 177Lu-PSMA-1: The study will begin with a safety run-in of 6 patients treated with 7.4 GBq of 177Lu-PSMA1 [starting activity], IV, q6W for 4 administrations.

If more than one patient experiences severe toxicity during the first cycle, then a lower activity of 177Lu-PSMA-1 will be evaluated in an additional cohort of 6 patients (5.9 GBq).

The 6 patients enrolled in this safety run-in step treated at the selected activity for phase II will be included in the evaluation of Phase II part.

• A Phase II part aiming to assess the clinical activity of 177Lu-PSMA-1

Patients will be treated and followed-up as following :

Selection step -68Ga-PSMA PET:

A selection step is mandatory for all patients in order to evaluate the PSMA expression in tumor lesions through 68Ga-PSMA PET and according to local imaging review. Only patients with PSMA expressing tumors will be eligible to the treatment step according eligbility

Treatment step:

Eligible patients will be treated with 177Lu-PSMA-1 (initial activity: 7.4 GBq), intravenously (IV) for 4 administrations every 6 weeks.

Assessment step:

To assess tumor response according to RECIST V1.1, imaging will be performed at baseline, at W9, at W24, then every 12 weeks up to 1 year after the first administration and then every 24 weeks until progression, death, loss to follow-up, or overall study completion, whichever is earliest. Survival status will be documented for all patients until death or overall study completion at least 12 months after the last patient. ;

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Neoplasms
• Metastatic Clear Cell Renal Cell Carcinoma

• NCT number: NCT06059014
• Study type: Interventional
• Source: Centre Leon Berard
• Contact: anne-laure Giraudet, Dr
• Phone: 0033469856001
• Email: annelaure.giraudet@lyon.unincancer.fr
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 9, 2023
• Completion date: April 2027