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

Brian M. Alexander; Paul D. Brown; Manmeet S. Ahluwalia; Hidefumi Aoyama; Brigitta G. Baumert; Susan M. Chang; Laurie E. Gaspar; Steven N. Kalkanis; David R. Macdonald; Minesh P. Mehta; Riccardo Soffietti; John H. Suh; Martin J. van den Bent; Michael A. Vogelbaum; Jeffrey S. Wefel; Eudocia Q. Lee; Patrick Y. Wen; Response Assessment Neuro-Oncology

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

Brian M. Alexander^*, Paul D. Brown, Manmeet S. Ahluwalia, Hidefumi Aoyama, Brigitta G. Baumert, Susan M. Chang, Laurie E. Gaspar, Steven N. Kalkanis, David R. Macdonald, Minesh P. Mehta, Riccardo Soffietti, John H. Suh, Martin J. van den Bent, Michael A. Vogelbaum, Jeffrey S. Wefel, Eudocia Q. Lee, Patrick Y. Wen, Response Assessment Neuro-Oncology

^*Corresponding author for this work

GROW - Innovative Cancer Diagnostics & Therapy

Research output: Contribution to journal › Review article › peer-review

25 Citations (Web of Science)

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.

Original language	English
Pages (from-to)	E33-E42
Number of pages	10
Journal	Lancet oncology
Volume	19
Issue number	1
DOIs	https://doi.org/10.1016/S1470-2045(17)30692-7
Publication status	Published - 1 Jan 2018

Keywords

QUALITY-OF-LIFE
STEREOTACTIC RADIOSURGERY
RADIATION-THERAPY
RANDOMIZED-TRIAL
RANO GROUP
NEUROCOGNITIVE FUNCTION
SURGICAL RESECTION
SINGLE METASTASES
RADIOTHERAPY
SURVIVAL

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10.1016/S1470-2045(17)30692-7

Cite this

Alexander, B. M., Brown, P. D., Ahluwalia, M. S., Aoyama, H., Baumert, B. G., Chang, S. M., Gaspar, L. E., Kalkanis, S. N., Macdonald, D. R., Mehta, M. P., Soffietti, R., Suh, J. H., van den Bent, M. J., Vogelbaum, M. A., Wefel, J. S., Lee, E. Q., Wen, P. Y., & Response Assessment Neuro-Oncology (2018). Clinical trial design for local therapies for brain metastases: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group. Lancet oncology, 19(1), E33-E42. https://doi.org/10.1016/S1470-2045(17)30692-7

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

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.",

keywords = "QUALITY-OF-LIFE, STEREOTACTIC RADIOSURGERY, RADIATION-THERAPY, RANDOMIZED-TRIAL, RANO GROUP, NEUROCOGNITIVE FUNCTION, SURGICAL RESECTION, SINGLE METASTASES, RADIOTHERAPY, SURVIVAL",

author = "Alexander, {Brian M.} and Brown, {Paul D.} and Ahluwalia, {Manmeet S.} and Hidefumi Aoyama and Baumert, {Brigitta G.} and Chang, {Susan M.} and Gaspar, {Laurie E.} and Kalkanis, {Steven N.} and Macdonald, {David R.} and Mehta, {Minesh P.} and Riccardo Soffietti and Suh, {John H.} and {van den Bent}, {Martin J.} and Vogelbaum, {Michael A.} and Wefel, {Jeffrey S.} and Lee, {Eudocia Q.} and Wen, {Patrick Y.} and {Response Assessment Neuro-Oncology}",

year = "2018",

month = jan,

day = "1",

doi = "10.1016/S1470-2045(17)30692-7",

language = "English",

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Alexander, BM, Brown, PD, Ahluwalia, MS, Aoyama, H, Baumert, BG, Chang, SM, Gaspar, LE, Kalkanis, SN, Macdonald, DR, Mehta, MP, Soffietti, R, Suh, JH, van den Bent, MJ, Vogelbaum, MA, Wefel, JS, Lee, EQ, Wen, PY & Response Assessment Neuro-Oncology 2018, 'Clinical trial design for local therapies for brain metastases: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group', Lancet oncology, vol. 19, no. 1, pp. E33-E42. https://doi.org/10.1016/S1470-2045(17)30692-7

TY - JOUR

T1 - Clinical trial design for local therapies for brain metastases

T2 - a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group

AU - Alexander, Brian M.

AU - Brown, Paul D.

AU - Ahluwalia, Manmeet S.

AU - Aoyama, Hidefumi

AU - Baumert, Brigitta G.

AU - Chang, Susan M.

AU - Gaspar, Laurie E.

AU - Kalkanis, Steven N.

AU - Macdonald, David R.

AU - Mehta, Minesh P.

AU - Soffietti, Riccardo

AU - Suh, John H.

AU - van den Bent, Martin J.

AU - Vogelbaum, Michael A.

AU - Wefel, Jeffrey S.

AU - Lee, Eudocia Q.

AU - Wen, Patrick Y.

AU - Response Assessment Neuro-Oncology

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - QUALITY-OF-LIFE

KW - STEREOTACTIC RADIOSURGERY

KW - RADIATION-THERAPY

KW - RANDOMIZED-TRIAL

KW - RANO GROUP

KW - NEUROCOGNITIVE FUNCTION

KW - SURGICAL RESECTION

KW - SINGLE METASTASES

KW - RADIOTHERAPY

KW - SURVIVAL

U2 - 10.1016/S1470-2045(17)30692-7

DO - 10.1016/S1470-2045(17)30692-7

M3 - Review article

VL - 19

SP - E33-E42

JO - Lancet oncology

JF - Lancet oncology

SN - 1470-2045

IS - 1

ER -