Phase I/II trial of meclofenamate in progressive MGMT-methylated glioblastoma under temozolomide second-line therapy—the MecMeth/NOA-24 trial

Research output: Contribution to journalResearch articleContributedpeer-review


  • Thomas Zeyen - , University of Bonn (Author)
  • Anna Laura Potthoff - , University of Bonn (Author)
  • Robert Nemeth - , University of Bonn (Author)
  • Dieter H. Heiland - , University of Freiburg (Author)
  • Michael C. Burger - , University Hospital Frankfurt (Author)
  • Joachim P. Steinbach - , University Hospital Frankfurt (Author)
  • Peter Hau - , University of Regensburg (Author)
  • Ghazaleh Tabatabai - , University of Tübingen (Author)
  • Martin Glas - , University of Duisburg-Essen (Author)
  • Uwe Schlegel - , Ruhr University Bochum (Author)
  • Oliver Grauer - , University of Münster (Author)
  • Dietmar Krex - , Department of Neurosurgery, University Hospital Carl Gustav Carus Dresden (Author)
  • Oliver Schnell - , University of Freiburg (Author)
  • Roland Goldbrunner - , University of Cologne (Author)
  • Michael Sabel - , Heinrich Heine University Düsseldorf (Author)
  • Niklas Thon - , Ludwig Maximilian University of Munich (Author)
  • Daniel Delev - , RWTH Aachen University (Author)
  • Hans Clusmann - , RWTH Aachen University (Author)
  • Clemens Seidel - , Leipzig University (Author)
  • Erdem Güresir - , University of Bonn (Author)
  • Matthias Schmid - , University of Bonn (Author)
  • Patrick Schuss - , University of Bonn (Author)
  • Frank A. Giordano - , University of Bonn (Author)
  • Alexander Radbruch - , University of Bonn (Author)
  • Albert Becker - , University of Bonn (Author)
  • Johannes Weller - , University of Bonn (Author)
  • Christina Schaub - , University of Bonn (Author)
  • Hartmut Vatter - , University of Bonn (Author)
  • Judith Schilling - , University of Bonn (Author)
  • Frank Winkler - , Heidelberg University  (Author)
  • Ulrich Herrlinger - , University of Bonn (Author)
  • Matthias Schneider - , University of Bonn (Author)


Background: 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. Methods: 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. Discussion: 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. Trial registration: EudraCT 2021-000708-39. Registered on 08 February 2021.


Original languageEnglish
Article number57
Issue number1
Publication statusPublished - Dec 2022



  • Glioblastoma, Meclofenamate, Relapse, Second-line therapy, Temozolomide