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Lancet Oncol. 2018 Jan;19(1):e33-e42. doi: 10.1016/S1470-2045(17)30692-7.

Clinical trial design for local therapies for brain metastases: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group.

Author information

1
Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: brian_alexander@dfci.harvard.edu.
2
Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
3
Rose Ella Burkhardt Brain Tumor and Neuro Oncology Center, Cleveland Clinic, Cleveland, OH, USA.
4
Department of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
5
Department of Radiation Oncology, Paracelsus Clinic Osnabrück, University of Münster, Münster, Germany; Department of Radiation Oncology (MAASTRO Clinic), Maastricht University Medical Centre, Maastricht, Netherlands.
6
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
7
Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, USA.
8
Henry Ford Health System, Wayne State University, Department of Neurosurgery, Detroit, MI, USA.
9
London Regional Cancer Program, London, ON, Canada.
10
Department of Radiation Oncology, Miami Cancer Institute, Miami, FL, USA.
11
Department of Neuro-Oncology, University of Turin and City of Health and Science Hospital, Turin, Italy.
12
Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA.
13
Brain Tumor Center, Erasmus MC, Rotterdam, Netherlands.
14
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
15
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA, USA.

Abstract

The goals of therapeutic and biomarker development form the foundation of clinical trial design, and change considerably from early-phase to late-phase trials. From these goals, decisions on specific clinical trial design elements, such as endpoint selection and statistical approaches, are formed. Whereas early-phase trials might focus on finding a therapeutic signal to make decisions on further development, late-phase trials focus on the confirmation of therapeutic impact by considering clinically meaningful endpoints. In this guideline from the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group, we highlight issues related to, and provide recommendations for, the design of clinical trials on local therapies for CNS metastases from solid tumours. We discuss endpoint selection criteria, the analysis appropriate for early-phase and late-phase trials, the association between tumour-specific and clinically meaningful endpoints, and possible issues related to the estimation of local control in the context of competing risks. In light of these discussions, we make specific recommendations on the clinical trial design of local therapies for brain metastases.

PMID:
29304360
DOI:
10.1016/S1470-2045(17)30692-7
[Indexed for MEDLINE]

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