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Phase I/II trial of meclofenamate in progressive MGMT-methylated glioblastoma under temozolomide second-line therapy-the MecMeth/NOA-24 trial.
- Source :
- Trials; 1/19/2022, Vol. 23 Issue 1, p1-16, 16p, 1 Diagram, 1 Chart, 1 Graph
- Publication Year :
- 2022
-
Abstract
- <bold>Background: </bold>Glioblastoma is the most frequent and malignant primary brain tumor. Even in the subgroup with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and favorable response to first-line therapy, survival after relapse is short (12 months). Standard therapy for recurrent MGMT-methylated glioblastoma is not standardized and may consist of re-resection, re-irradiation, and chemotherapy with temozolomide (TMZ), lomustine (CCNU), or a combination thereof. Preclinical results show that meclofenamate (MFA), originally developed as a nonsteroidal anti-inflammatory drug (NSAID) and registered in the USA, sensitizes glioblastoma cells to temozolomide-induced toxicity via inhibition of gap junction-mediated intercellular cytosolic traffic and demolishment of tumor microtube (TM)-based network morphology.<bold>Methods: </bold>In this study, combined MFA/TMZ therapy will be administered (orally) in patients with first relapse of MGMT-methylated glioblastoma. A phase I component (6-12 patients, 2 dose levels of MFA + standard dose TMZ) evaluates safety and feasibility and determines the dose for the randomized phase II component (2 × 30 patients) with progression-free survival as the primary endpoint.<bold>Discussion: </bold>This study is set up to assess toxicity and first indications of efficacy of MFA repurposed in the setting of a very difficult-to-treat recurrent tumor. The trial is a logical next step after the identification of the role of resistance-providing TMs in glioblastoma, and results will be crucial for further trials targeting TMs. In case of favorable results, MFA may constitute the first clinically feasible TM-targeted drug and therefore might bridge the idea of a TM-targeted therapeutic approach from basic insights into clinical reality.<bold>Trial Registration: </bold>EudraCT 2021-000708-39 . Registered on 08 February 2021. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17456215
- Volume :
- 23
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Trials
- Publication Type :
- Academic Journal
- Accession number :
- 154765216
- Full Text :
- https://doi.org/10.1186/s13063-021-05977-0