TY - JOUR
T1 - Phase 2 trial design in neuro-oncology revisited
T2 - A report from the RANO group
AU - Galanis, Evanthia
AU - Wu, Wenting
AU - Cloughesy, Timothy
AU - Lamborn, Kathleen
AU - Mann, Bhupinder
AU - Wen, Patrick Y.
AU - Reardon, David A.
AU - Wick, Wolfgang
AU - Macdonald, David
AU - Armstrong, Terri S.
AU - Weller, Michael
AU - Vogelbaum, Michael
AU - Colman, Howard
AU - Sargent, Daniel J.
AU - van den Bent, Martin J.
AU - Gilbert, Mark
AU - Chang, Susan
N1 - Funding Information:
MJvdB has a consultant role with Roche, MSD, Siena Biotech, Antisense Pharma, and Merck Ag; and has received honoraria from MSD and research funding from Roche. MV has a consultant role with Merck, Bristol-Myers Squibb, and Pharmaco-kinesis. TC has a consultant role with Genentech/Roche, Lilly, Novartis, and Agio; and has received honoraria from Merck. PYW has a consultant role with Novartis, Merck, and Stemline Therapeutics; and has received honoraria from Merck and research support from Novartis, Amgen, AstraZeneca, Sanofi-Aventis, Genentech, Vascular Biogenics, Esai, and Exelixis. DAR has a consultant role with Genentech/Roche, EMD Serono, and Merck/Schering; and has received honoraria from Genentech/Roche, EMD Serono, and Merck/Schering. WWi has a consultant role with Roche, Magforce, and MSD; and has received honoraria from MSD and research funding from MSD and Boehinger-Ingelheim. TSA has received honoraria from Merck and research funding from Merck and Genentech. MW has a consultant role with Roche, Merck, and SMD; and has received research funding from Roche and Merck Serono. HC has a consultant role with Castle Biosciences and has received research funding from Bayer Onyx and Myrexis. MG has a consultant role with Genentech, Merck, and Abbott; and has received honoraria and research funding from Merck and Genentech. SC has received research funding from Novartis and Schering. DM has received honoraria from Merck and Roche. EG, WWu, DJS, KL, and BM declare that they have no conflicts of interest in relation to this manuscript.
PY - 2012/5
Y1 - 2012/5
N2 - Advances in the management of gliomas, including the approval of agents such as temozolomide and bevacizumab, have created an evolving therapeutic landscape in glioma treatment, thus affecting our ability to reliably use historical controls to comparatively assess the activity of new therapies. Furthermore, the increasing availability of novel, targeted agents-which are competing for a small patient population, in view of the low incidence of primary brain tumours-draws attention to the need to improve the efficiency of phase 2 clinical testing in neuro-oncology to expeditiously transition the most promising of these drugs or combinations to potentially practice-changing phase 3 trials. In this report from the Response Assessment in Neurooncology (RANO) group, we review phase 2 trial designs that can address these challenges and capitalise on scientific and clinical advances in brain tumour treatment in neuro-oncology to accelerate and optimise the selection of drugs deserving further testing in phase 3 trials. Although there is still a small role for single-arm and non-comparative phase 2 designs, emphasis is placed on the potential role that comparative randomised phase 2 designs-such as screening designs, selection designs, discontinuation designs, and adaptive designs, including seamless phase 2/3 designs-can have. The rational incorporation of these designs, as determined by the specific clinical setting and the trial's endpoints or goals, has the potential to substantially advance new drug development in neuro-oncology.
AB - Advances in the management of gliomas, including the approval of agents such as temozolomide and bevacizumab, have created an evolving therapeutic landscape in glioma treatment, thus affecting our ability to reliably use historical controls to comparatively assess the activity of new therapies. Furthermore, the increasing availability of novel, targeted agents-which are competing for a small patient population, in view of the low incidence of primary brain tumours-draws attention to the need to improve the efficiency of phase 2 clinical testing in neuro-oncology to expeditiously transition the most promising of these drugs or combinations to potentially practice-changing phase 3 trials. In this report from the Response Assessment in Neurooncology (RANO) group, we review phase 2 trial designs that can address these challenges and capitalise on scientific and clinical advances in brain tumour treatment in neuro-oncology to accelerate and optimise the selection of drugs deserving further testing in phase 3 trials. Although there is still a small role for single-arm and non-comparative phase 2 designs, emphasis is placed on the potential role that comparative randomised phase 2 designs-such as screening designs, selection designs, discontinuation designs, and adaptive designs, including seamless phase 2/3 designs-can have. The rational incorporation of these designs, as determined by the specific clinical setting and the trial's endpoints or goals, has the potential to substantially advance new drug development in neuro-oncology.
UR - http://www.scopus.com/inward/record.url?scp=84860487114&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860487114&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(11)70406-5
DO - 10.1016/S1470-2045(11)70406-5
M3 - Review article
C2 - 22554547
AN - SCOPUS:84860487114
SN - 1470-2045
VL - 13
SP - e196-e204
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 5
ER -