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. 2023 Apr 15;23(1):344.
doi: 10.1186/s12885-023-10829-y.

Phase I/II study testing the combination of AGuIX nanoparticles with radiochemotherapy and concomitant temozolomide in patients with newly diagnosed glioblastoma (NANO-GBM trial protocol)

Emilie Thivat  1   2   3 , Mélanie Casile  4   5   6 , Juliette Moreau  5   6   7 , Ioana Molnar  4   5   6 , Sandrine Dufort  8 , Khalide Seddik  8 , Géraldine Le Duc  8 , Olivier De Beaumont  8 , Markus Loeffler  8 , Xavier Durando  4   5   6   9 , Julian Biau  5   6   7
Affiliations

Phase I/II study testing the combination of AGuIX nanoparticles with radiochemotherapy and concomitant temozolomide in patients with newly diagnosed glioblastoma (NANO-GBM trial protocol)

Emilie Thivat et al. BMC Cancer. .

Abstract

Background: Despite standard treatments including chemoradiotherapy with temozolomide (TMZ) (STUPP protocol), the prognosis of glioblastoma patients remains poor. AGuIX nanoparticles have a high radiosensitizing potential, a selective and long-lasting accumulation in tumors and a rapid renal elimination. Their therapeutic effect has been proven in vivo on several tumor models, including glioblastoma with a potential synergetic effect when combined with TMZ based chemoradiotherapy, and they are currently evaluated in 4 ongoing Phase Ib and II clinical trials in 4 indications (brain metastases, lung, pancreatic and cervix cancers) (> 100 patients received AGuIX). Thus, they could offer new perspectives for patients with newly diagnosed glioblastoma. The aim of this study is to determine the recommended dose of AGuIX as a radiosensitizer in combination with radiotherapy and TMZ during the concurrent radio-chemotherapy period for phase II (RP2D) and to estimate the efficacy of the combination.

Methods: NANO-GBM is a multicenter, phase I/II, randomized, open-label, non-comparative, therapeutic trial. According to a dose escalation scheme driven by a TITE-CRM design, 3 dose levels of AGuIX (50, 75 and 100 mg/kg) will be tested in phase I added to standard concomitant radio-chemotherapy. Patients with grade IV glioblastoma, not operated or partially operated, with a KPS ≥ 70% will be eligible for the study. The primary endpoints are i) for phase I, the RP2D of AGuIX, with DLT defined as any grade 3-4 NCI-CTCAE toxicity and ii) for phase II, the 6-month progression-free survival rate. The pharmacokinetics, distribution of nanoparticles, tolerance of the combination, neurological status, overall survival (median, 6-month and 12-month rates), response to treatment, and progression-free survival (median and 12-month rates) will be assessed as secondary objectives. Maximum sixty-six patients are expected to be recruited in the study from 6 sites.

Discussion: The use of AGuIX nanoparticles could allow to overpass the radioresistance to the reference treatment of newly diagnosed glioblastomas that have the poorest prognosis (incomplete resection or biopsy only).

Trial registration: Clinicaltrials.gov: NCT04881032 , registered on April 30, 2021. Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°Eudra CT 2020-004552-15.

Protocol: version 3, 23 May 2022.

Keywords: AGuIX; Glioblastoma; Nanomedicine; Nanoparticles; Radiosensitization; Radiotherapy.

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Conflict of interest statement

GLD discloses patent No. WO2009/053644 which protects the AGuIX nanoparticles described in this publication. SD, KS, ML, ODB and GLD are employees of NH TherAguix (Meylan, France), which is developing the AGuIX nanoparticles. SD, ML and GLD own shares in this company. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Overview of the treatment period of the NANO-GBM study
See this image and copyright information in PMC

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