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@ARTICLE{Moreno:275251,
      author       = {L. Moreno and S. G. DuBois and J. Glade Bender and A.
                      Mauguen and N. Bird and V. Buenger and M. Casanova and F.
                      Doz and E. Fox and L. Gore and D. S. Hawkins and S. Izraeli
                      and D. Jones$^*$ and P. R. Kearns and J. J. Molenaar and K.
                      Nysom and S. Pfister$^*$ and G. Reaman and M. Smith and B.
                      Weigel and G. Vassal and C. M. Zwaan and X. Paoletti and A.
                      Iasonos and A. D. J. Pearson},
      title        = {{C}ombination {E}arly-{P}hase {T}rials of {A}nticancer
                      {A}gents in {C}hildren and {A}dolescents.},
      journal      = {Journal of clinical oncology},
      volume       = {41},
      number       = {18},
      issn         = {0732-183X},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2023-00698},
      pages        = {3408-3422},
      year         = {2023},
      note         = {2023 Jun 20;41(18):3408-3422},
      abstract     = {There is an increasing need to evaluate innovative drugs
                      for childhood cancer using combination strategies. Strong
                      biological rationale and clinical experience suggest that
                      multiple agents will be more efficacious than monotherapy
                      for most diseases and may overcome resistance mechanisms and
                      increase synergy. The process to evaluate these combination
                      trials needs to maximize efficiency and should be agreed by
                      all stakeholders.After a review of existing combination
                      trial methodologies, regulatory requirements, and current
                      results, a consensus among stakeholders was
                      achieved.Combinations of anticancer therapies should be
                      developed on the basis of mechanism of action and robust
                      preclinical evaluation, and may include data from adult
                      clinical trials. The general principle for combination
                      early-phase studies is that, when possible, clinical trials
                      should be dose- and schedule-confirmatory rather than
                      dose-exploratory, and every effort should be made to
                      optimize doses early. Efficient early-phase combination
                      trials should be seamless, including dose confirmation and
                      randomized expansion. Dose evaluation designs for
                      combinations depend on the extent of previous knowledge. If
                      not previously evaluated, limited evaluation of monotherapy
                      should be included in the same clinical trial as the
                      combination. Randomized evaluation of a new agent plus
                      standard therapy versus standard therapy is the most
                      effective approach to isolate the effect and toxicity of the
                      novel agent. Platform trials may be valuable in the
                      evaluation of combination studies. Patient advocates and
                      regulators should be engaged with investigators early in a
                      proposed clinical development pathway and trial design must
                      consider regulatory requirements.An optimized, agreed
                      approach to the design and evaluation of early-phase
                      pediatric combination trials will accelerate drug
                      development and benefit all stakeholders, most importantly
                      children and adolescents with cancer.},
      subtyp        = {Review Article},
      cin          = {B360 / B062},
      ddc          = {610},
      cid          = {I:(DE-He78)B360-20160331 / I:(DE-He78)B062-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37015036},
      doi          = {10.1200/JCO.22.02430},
      url          = {https://inrepo02.dkfz.de/record/275251},
}