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@ARTICLE{Wick:140850,
      author       = {W. Wick$^*$ and S. Dettmer$^*$ and A. Berberich$^*$ and T.
                      Kessler$^*$ and I. Karapanagiotou-Schenkel$^*$ and A. Wick
                      and F. Winkler$^*$ and E. Pfaff$^*$ and B. Brors$^*$ and J.
                      Debus$^*$ and A. Unterberg and M. Bendszus and C.
                      Herold-Mende and A. Eisenmenger$^*$ and A. von Deimling$^*$
                      and D. Jones$^*$ and S. Pfister$^*$ and F. Sahm$^*$ and M.
                      Platten$^*$},
      title        = {{N}2{M}2 ({NOA}20) phase {I}/{II} trial of molecularly
                      matched targeted therapies plus radiotherapy in patients
                      with newly diagnosed non-{MGMT} hypermethylated
                      glioblastoma.},
      journal      = {Neuro-Oncology},
      volume       = {21},
      number       = {1},
      issn         = {1523-5866},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2018-01605},
      pages        = {95-105},
      year         = {2019},
      abstract     = {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.},
      cin          = {B320 / E050 / B062 / B330 / B300 / D170 / B360 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)B320-20160331 / I:(DE-He78)E050-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)B330-20160331 /
                      I:(DE-He78)B300-20160331 / I:(DE-He78)D170-20160331 /
                      I:(DE-He78)B360-20160331 / I:(DE-He78)L101-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30277538},
      doi          = {10.1093/neuonc/noy161},
      url          = {https://inrepo02.dkfz.de/record/140850},
}