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Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma
PURPOSE: Adequately prioritizing the numerous therapies and biomarkers available in late-stage testing for patients with glioblastoma (GBM) requires an efficient clinical testing platform. We developed and implemented INSIGhT (Individualized Screening Trial of Innovative Glioblastoma Therapy) as a n...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Clinical Oncology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448806/ https://www.ncbi.nlm.nih.gov/pubmed/32914038 http://dx.doi.org/10.1200/PO.18.00071 |
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author | Alexander, Brian M. Trippa, Lorenzo Gaffey, Sarah Arrillaga-Romany, Isabel C. Lee, Eudocia Q. Rinne, Mikael L. Ahluwalia, Manmeet S. Colman, Howard Fell, Geoffrey Galanis, Evanthia de Groot, John Drappatz, Jan Lassman, Andrew B. Meredith, David M. Nabors, L. Burt Santagata, Sandro Schiff, David Welch, Mary R. Ligon, Keith L. Wen, Patrick Y. |
author_facet | Alexander, Brian M. Trippa, Lorenzo Gaffey, Sarah Arrillaga-Romany, Isabel C. Lee, Eudocia Q. Rinne, Mikael L. Ahluwalia, Manmeet S. Colman, Howard Fell, Geoffrey Galanis, Evanthia de Groot, John Drappatz, Jan Lassman, Andrew B. Meredith, David M. Nabors, L. Burt Santagata, Sandro Schiff, David Welch, Mary R. Ligon, Keith L. Wen, Patrick Y. |
author_sort | Alexander, Brian M. |
collection | PubMed |
description | PURPOSE: Adequately prioritizing the numerous therapies and biomarkers available in late-stage testing for patients with glioblastoma (GBM) requires an efficient clinical testing platform. We developed and implemented INSIGhT (Individualized Screening Trial of Innovative Glioblastoma Therapy) as a novel adaptive platform trial (APT) to develop precision medicine approaches in GBM. METHODS: INSIGhT compares experimental arms with a common control of standard concurrent temozolomide and radiation therapy followed by adjuvant temozolomide. The primary end point is overall survival. Patients with newly diagnosed unmethylated GBM who are IDH R132H mutation negative and with genomic data available for biomarker grouping are eligible. At the initiation of INSIGhT, three experimental arms (neratinib, abemaciclib, and CC-115), each with a proposed genomic biomarker, are tested simultaneously. Initial randomization is equal across arms. As the trial progresses, randomization probabilities adapt on the basis of accumulating results using Bayesian estimation of the biomarker-specific probability of treatment impact on progression-free survival. Treatment arms may drop because of low probability of treatment impact on overall survival, and new arms may be added. Detailed information on the statistical model and randomization algorithm is provided to stimulate discussion on trial design choices more generally and provide an example for other investigators developing APTs. CONCLUSION: INSIGhT (NCT02977780) is an ongoing novel biomarker-based, Bayesian APT for patients with newly diagnosed unmethylated GBM. Our goal is to dramatically shorten trial execution timelines while increasing scientific power of results and biomarker discovery using adaptive randomization. We anticipate that trial execution efficiency will also be improved by using the APT format, which allows for the collaborative addition of new experimental arms while retaining the overall trial structure. |
format | Online Article Text |
id | pubmed-7448806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Society of Clinical Oncology |
record_format | MEDLINE/PubMed |
spelling | pubmed-74488062020-09-09 Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma Alexander, Brian M. Trippa, Lorenzo Gaffey, Sarah Arrillaga-Romany, Isabel C. Lee, Eudocia Q. Rinne, Mikael L. Ahluwalia, Manmeet S. Colman, Howard Fell, Geoffrey Galanis, Evanthia de Groot, John Drappatz, Jan Lassman, Andrew B. Meredith, David M. Nabors, L. Burt Santagata, Sandro Schiff, David Welch, Mary R. Ligon, Keith L. Wen, Patrick Y. JCO Precis Oncol Special Article PURPOSE: Adequately prioritizing the numerous therapies and biomarkers available in late-stage testing for patients with glioblastoma (GBM) requires an efficient clinical testing platform. We developed and implemented INSIGhT (Individualized Screening Trial of Innovative Glioblastoma Therapy) as a novel adaptive platform trial (APT) to develop precision medicine approaches in GBM. METHODS: INSIGhT compares experimental arms with a common control of standard concurrent temozolomide and radiation therapy followed by adjuvant temozolomide. The primary end point is overall survival. Patients with newly diagnosed unmethylated GBM who are IDH R132H mutation negative and with genomic data available for biomarker grouping are eligible. At the initiation of INSIGhT, three experimental arms (neratinib, abemaciclib, and CC-115), each with a proposed genomic biomarker, are tested simultaneously. Initial randomization is equal across arms. As the trial progresses, randomization probabilities adapt on the basis of accumulating results using Bayesian estimation of the biomarker-specific probability of treatment impact on progression-free survival. Treatment arms may drop because of low probability of treatment impact on overall survival, and new arms may be added. Detailed information on the statistical model and randomization algorithm is provided to stimulate discussion on trial design choices more generally and provide an example for other investigators developing APTs. CONCLUSION: INSIGhT (NCT02977780) is an ongoing novel biomarker-based, Bayesian APT for patients with newly diagnosed unmethylated GBM. Our goal is to dramatically shorten trial execution timelines while increasing scientific power of results and biomarker discovery using adaptive randomization. We anticipate that trial execution efficiency will also be improved by using the APT format, which allows for the collaborative addition of new experimental arms while retaining the overall trial structure. American Society of Clinical Oncology 2019-03-27 /pmc/articles/PMC7448806/ /pubmed/32914038 http://dx.doi.org/10.1200/PO.18.00071 Text en © 2019 by American Society of Clinical Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Special Article Alexander, Brian M. Trippa, Lorenzo Gaffey, Sarah Arrillaga-Romany, Isabel C. Lee, Eudocia Q. Rinne, Mikael L. Ahluwalia, Manmeet S. Colman, Howard Fell, Geoffrey Galanis, Evanthia de Groot, John Drappatz, Jan Lassman, Andrew B. Meredith, David M. Nabors, L. Burt Santagata, Sandro Schiff, David Welch, Mary R. Ligon, Keith L. Wen, Patrick Y. Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma |
title | Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma |
title_full | Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma |
title_fullStr | Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma |
title_full_unstemmed | Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma |
title_short | Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma |
title_sort | individualized screening trial of innovative glioblastoma therapy (insight): a bayesian adaptive platform trial to develop precision medicines for patients with glioblastoma |
topic | Special Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448806/ https://www.ncbi.nlm.nih.gov/pubmed/32914038 http://dx.doi.org/10.1200/PO.18.00071 |
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