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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Clinical Oncology 2019
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.
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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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