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Zeyen, Thomas; Potthoff, Anna-Laura; Nemeth, Robert; Heiland, Dieter H.; Burger, Michael C.; Steinbach, Joachim P.; Hau, Peter; Tabatabai, Ghazaleh; Glas, Martin; Schlegel, Uwe; Grauer, Oliver; Krex, Dietmar; Schnell, Oliver; Goldbrunner, Roland; Sabel, Michael; Thon, Niklas; Delev, Daniel; Clusmann, Hans; Seidel, Clemens; Güresir, Erdem; Schmid, Matthias; Schuss, Patrick; Giordano, Frank A.; Radbruch, Alexander; [...]

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

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  • Medientyp: E-Artikel
  • Titel: Phase I/II trial of meclofenamate in progressive MGMT-methylated glioblastoma under temozolomide second-line therapy—the MecMeth/NOA-24 trial
  • Beteiligte: Zeyen, Thomas; Potthoff, Anna-Laura; Nemeth, Robert; Heiland, Dieter H.; Burger, Michael C.; Steinbach, Joachim P.; Hau, Peter; Tabatabai, Ghazaleh; Glas, Martin; Schlegel, Uwe; Grauer, Oliver; Krex, Dietmar; Schnell, Oliver; Goldbrunner, Roland; Sabel, Michael; Thon, Niklas; Delev, Daniel; Clusmann, Hans; Seidel, Clemens; Güresir, Erdem; Schmid, Matthias; Schuss, Patrick; Giordano, Frank A.; Radbruch, Alexander; [...]
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: Trials
  • Sprache: Englisch
  • DOI: 10.1186/s13063-021-05977-0
  • ISSN: 1745-6215
  • Schlagwörter: Pharmacology (medical) ; Medicine (miscellaneous)
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Discussion</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Trial registration</jats:title> <jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.clinicaltrialsregister.eu/ctr-search/search?query=2021-000708-39">EudraCT 2021-000708-39</jats:ext-link>. Registered on 08 February 2021</jats:p> </jats:sec>
  • Zugangsstatus: Freier Zugang