TY  - JOUR
AU  - Wick, Wolfgang
AU  - Dettmer, Susan
AU  - Berberich, Anne
AU  - Kessler, Tobias
AU  - Karapanagiotou-Schenkel, Irini
AU  - Wick, Antje
AU  - Winkler, Frank
AU  - Pfaff, Elke
AU  - Brors, Benedikt
AU  - Debus, Jürgen
AU  - Unterberg, Andreas
AU  - Bendszus, Martin
AU  - Herold-Mende, Christel
AU  - Eisenmenger, Andreas
AU  - von Deimling, Andreas
AU  - Jones, David
AU  - Pfister, Stefan
AU  - Sahm, Felix
AU  - Platten, Michael
TI  - N2M2 (NOA20) phase I/II trial of molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed non-MGMT hypermethylated glioblastoma.
JO  - Neuro-Oncology
VL  - 21
IS  - 1
SN  - 1523-5866
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2018-01605
SP  - 95-105
PY  - 2019
AB  - Patients with glioblastoma without O6-methyl guanine O6-methylatransferase (MGMT) promoter hypermethylation are unlikely to benefit from alkylating chemotherapy with temozolomide (TMZ). Trials aiming at replacing TMZ with targeted agents in unselected patient populations have failed to demonstrate any improvement of survival. Advances in molecular understanding and diagnostic precision enable identification of key genetic alterations in a timely manner and in principle allow treatments with targeted compounds based on molecular markers.The NCT Neuro Master Match (N2M2) trial is an open label multicenter phase I/IIa umbrella trial for patients with newly diagnosed isocitrate dehydrogenase (IDH) wildtype glioblastoma without MGMT promoter hypermethylation to show safety, feasibility and preliminary efficacy of treatment with targeted compounds in addition to standard radiotherapy based on molecular characterization. N2M2 is formally divided in a DISCOVERY and a TREATMENT part. DISCOVERY includes broad molecular neuropathological diagnostics to detect predefined biomarkers for targeted treatments. Molecular diagnostics and bioinformatic evaluation are performed within four weeks, allowing a timely initiation of postoperative treatment. Stratification for TREATMENT takes place in five subtrials, including alectinib, idasanutlin, palbociclib, vismodegib and temsirolimus as targeted therapies, according to the best matching molecular alteration. Patients without matching alterations are randomized between subtrials without strong biomarkers using atezolizumab and asinercept (APG101), and the standard of care, TMZ. For the phase I parts, a Bayesian criterion is used for continuous monitoring of toxicity. In the phase II trials, progression-free survival at six months is used as endpoint for efficacy.
LB  - PUB:(DE-HGF)16
C6  - pmid:30277538
DO  - DOI:10.1093/neuonc/noy161
UR  - https://inrepo02.dkfz.de/record/140850
ER  -