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

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

开始日期2023-11-09

申办/合作机构

Centre Léon Bérard Lyon et Rhône-Alpes

100 项与 177Lu-PSMA-1 相关的临床结果

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100 项与 177Lu-PSMA-1 相关的转化医学

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100 项与 177Lu-PSMA-1 相关的专利（医药）

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项与 177Lu-PSMA-1 相关的文献（医药）

2023-02-01·Clinical Nuclear Medicine

Unintentional Intra-arterial Injection of 177Lu-PSMA-1 in a Patient With a Peritoneal Carcinosis Secondary to a Metastatic Prostate Cancer

Article

作者: Giraudet, Anne Laure ; Kryza, David ; Mognetti, Thomas ; Badel, Jean Noël ; Moreau, Aurélie

AbstractWe report the case of an 81-year-old man presenting with peritoneal carcinosis secondary to a metastatic castrate-resistant prostate cancer addressed for 177Lu-PSMA-1 therapy. During the second cycle, a diffuse uptake in his left forearm was observed on the 1-hour postinjection scintigraphy, typical for an accidental intra-arterial injection. Less than 24 hours postinjection, a full removal of the intra-arterial injection was observed in the man, without any pain or symptoms. Moreover, the man demonstrated an 85% PSA reduction and a CT OR following the RECIST 1.1 criteria after 3 cycles.

BMC Cancer

A multicentric, single arm, open-label, phase I/II study evaluating PSMA targeted radionuclide therapy in adult patients with metastatic clear cell renal cancer (PRadR)

Article

作者: Tatu, Delphine ; Giraudet, Anne-Laure ; Cropet, Claire ; Kryza, David ; Garin, Gwenaelle ; Perol, David ; Bidaux, Anne-Sophie ; Vinceneux, Armelle ; Badel, Jean-Noël

AbstractBackgroundDespite advancements in managing metastatic clear cell renal carcinoma (mccRCC) through antiangiogenic tyrosine kinase inhibitors and immunotherapy, there remains a demand for novel treatments for patients experiencing progression despite the use of these medications. There is currently no established standard treatment for patients receiving third therapy line. Prostate Specific Membrane Antigen (PSMA) whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma is also highly expressed in neovessels of various solid tumors including renal cell carcinoma (RCC): 86% of clear cell RCC, 61% of chromophobe RCC, and 28% of papillary RCC. Therefore, 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.MethodsThis is a multicenter phase I/II study designed to assess the tolerability and effectiveness of 177Lu-PSMA-1 in individuals with PSMA-positive metastatic clear cell renal cell carcinoma (ccRCC), identified through 68Ga-PSMA PET, conducted in France (PRadR). 48 patients will be treated with 4 cycles of 7.4 GBq of 177Lu-PSMA-1 every 6 weeks. The primary objective is to evaluate the safety of 177Lu-PSMA-1 (phase I) and the efficacy of 177Lu-PSMA-1 in mccRCC patients (phase II). Primary endpoints are incidence of Severe Toxicities (ST) occurring during the first cycle (i.e. 6 first weeks) and disease Control Rate after 24 weeks of treatment (DCR24w) as per RECIST V1.1. Secondary objective is to further document the clinical activity of 177Lu-PSMA-1 in mccRCC patients (duration of response (DoR), best overall response rate (BORR), progression fee survival (PFS) and overall survival (OS).DiscussionOur prospective study may lead to new potential indications for the use of 177Lu-PSMA-1 in mccRCC patients and should confirm the efficacy and safety of this radionuclide therapy with limited adverse events. The use of 177Lu-PSMA-1may lead to increase disease control, objective response rate and the quality of life in mccRCC patients.Trial registrationClinicalTrials.gov: NCT06059014.

Pharmaceuticals

Development and Validation of Analytical Methods for Radiochemical Purity of 177Lu-PSMA-1

Article

作者: Piquemal, Marie ; Djaileb, Loïc ; Desruet, Marie-Dominique ; Orhon, Pauline ; Leenhardt, Julien ; Bedouch, Pierrick ; Vuillez, Jean-Philippe ; De Leiris, Nicolas

Prostate Specific Membrane Antigen (PSMA) is a highly relevant target in nuclear medicine due to its overexpression in prostate cancer. The 68Ga/177Lu-PSMA-1 combination is a theranostic agent for the detection and treatment of tumors overexpressing the PSMA target. Specifically, 177Lu-PSMA-1 is used in the treatment of castration-resistant prostate cancer that is ineffective or intolerant to the latest generation of chemotherapy and/or hormone therapy. This radiopharmaceutical is manufactured in a radiopharmaceutical synthesizing unit and must pass a quality control where the radiochemical purity (RCP) is assessed prior to release of the batch. RCP evaluation is performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Since there is no monograph for 177Lu-PSMA-1 in the European Pharmacopoeia, we validate the analytical methods according to the EANM recommendations adapted from ICH Q2. Specificity, linearity, accuracy, precision, intermediate precision, limit of quantification (LOQ) and robustness were described for HPLC and TLC in this study. The results obtained demonstrated the robustness and reliability of the HPLC and TLC analytical methods for the evaluation of the RCP of 177Lu-PSMA-1.

100 项与 177Lu-PSMA-1 相关的药物交易

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