The clinical trials landscape for glioblastoma: Is it adequate to develop new treatments?

Alyssa M. Vanderbeek; Rifaquat Rahman; Geoffrey Fell; Steffen Ventz; Tianqi Chen; Robert Redd; Giovanni Parmigiani; Timothy F. Cloughesy; Patrick Y. Wen; Lorenzo Trippa; Brian M. Alexander

doi:10.1093/neuonc/noy027

The clinical trials landscape for glioblastoma: Is it adequate to develop new treatments?

Alyssa M. Vanderbeek, Rifaquat Rahman, Geoffrey Fell, Steffen Ventz, Tianqi Chen, Robert Redd, Giovanni Parmigiani, Timothy F. Cloughesy, Patrick Y. Wen, Lorenzo Trippa, Brian M. Alexander

Research output: Contribution to journal › Article › peer-review

99 Scopus citations

Abstract

Background There have been few treatment advances for patients with glioblastoma (GBM) despite increasing scientific understanding of the disease. While factors such as intrinsic tumor biology and drug delivery are challenges to developing efficacious therapies, it is unclear whether the current clinical trial landscape is optimally evaluating new therapies and biomarkers. Methods We queried ClinicalTrials.gov for interventional clinical trials for patients with GBM initiated between January 2005 and December 2016 and abstracted data regarding phase, status, start and end dates, testing locations, endpoints, experimental interventions, sample size, clinical presentation/indication, and design to better understand the clinical trials landscape. Results Only approximately 8%-11% of patients with newly diagnosed GBM enroll on clinical trials with a similar estimate for all patients with GBM. Trial duration was similar across phases with median time to completion between 3 and 4 years. While 93% of clinical trials were in phases I-II, 26% of the overall clinical trial patient population was enrolled on phase III studies. Of the 8 completed phase III trials, only 1 reported positive results. Although 58% of the phase III trials were supported by phase II data with a similar endpoint, only 25% of these phase II trials were randomized. Conclusions The clinical trials landscape for GBM is characterized by long development times, inadequate dissemination of information, suboptimal go/no-go decision making, and low patient participation.

Original language	English (US)
Pages (from-to)	1034-1043
Number of pages	10
Journal	Neuro-Oncology
Volume	20
Issue number	8
DOIs	https://doi.org/10.1093/neuonc/noy027
State	Published - Jul 5 2018
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by a Burroughs Wellcome Innovations in Regulatory Science Award.

Funding Information:
Conflict of interest statement. P.Y.W. reports grants, personal fees and nonfinancial support from Agios and Novartis, nonfinancial support from Angiochem, GlaxoSmithKline, ImmunoCellular Therapeutics, VBI Vaccines, and Karyopharm and personal fees and nonfinancial support from AstraZeneca, Genentech/Roche, and Vascular Biogenics, grants and nonfinancial support from Merck, and nonfinancial support from Oncoceutics, Sanofi Aventis, personal fees from Cavion, INSYS Therapeutics, Monteris, from Novogen, Regeneron Pharmaceuticals, and Tocagen. T.F.C. reports consulting fees from: Roche/Genentech, VBL, Merck, BMS, Pfizer, Agios, Novogen, Boston Biomedical, MedQIA, Tocagen, Cortice Biosciences, Novocure, NewGen, Oxigene, Wellcome Trust, Sunovion Pharmaceuticals, Abbvie, Celgene, Lilly; and reports equity in Notable Labs. B.M.A. is the PI of INSIGhT, and adaptive platform trial supported by Eli Lilly, Celgene, and Puma and is the President and CEO of Global Coalition for Adaptive Research.

Publisher Copyright:
© 2017 The Author(s).

Keywords

clinical trials
glioblastoma
regulatory science

Publisher link

10.1093/neuonc/noy027

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@article{8c11e8c6afed4451938722af0995b15e,

title = "The clinical trials landscape for glioblastoma: Is it adequate to develop new treatments?",

abstract = "Background There have been few treatment advances for patients with glioblastoma (GBM) despite increasing scientific understanding of the disease. While factors such as intrinsic tumor biology and drug delivery are challenges to developing efficacious therapies, it is unclear whether the current clinical trial landscape is optimally evaluating new therapies and biomarkers. Methods We queried ClinicalTrials.gov for interventional clinical trials for patients with GBM initiated between January 2005 and December 2016 and abstracted data regarding phase, status, start and end dates, testing locations, endpoints, experimental interventions, sample size, clinical presentation/indication, and design to better understand the clinical trials landscape. Results Only approximately 8%-11% of patients with newly diagnosed GBM enroll on clinical trials with a similar estimate for all patients with GBM. Trial duration was similar across phases with median time to completion between 3 and 4 years. While 93% of clinical trials were in phases I-II, 26% of the overall clinical trial patient population was enrolled on phase III studies. Of the 8 completed phase III trials, only 1 reported positive results. Although 58% of the phase III trials were supported by phase II data with a similar endpoint, only 25% of these phase II trials were randomized. Conclusions The clinical trials landscape for GBM is characterized by long development times, inadequate dissemination of information, suboptimal go/no-go decision making, and low patient participation.",

keywords = "clinical trials, glioblastoma, regulatory science",

author = "Vanderbeek, {Alyssa M.} and Rifaquat Rahman and Geoffrey Fell and Steffen Ventz and Tianqi Chen and Robert Redd and Giovanni Parmigiani and Cloughesy, {Timothy F.} and Wen, {Patrick Y.} and Lorenzo Trippa and Alexander, {Brian M.}",

note = "Funding Information: This work was supported by a Burroughs Wellcome Innovations in Regulatory Science Award. Funding Information: Conflict of interest statement. P.Y.W. reports grants, personal fees and nonfinancial support from Agios and Novartis, nonfinancial support from Angiochem, GlaxoSmithKline, ImmunoCellular Therapeutics, VBI Vaccines, and Karyopharm and personal fees and nonfinancial support from AstraZeneca, Genentech/Roche, and Vascular Biogenics, grants and nonfinancial support from Merck, and nonfinancial support from Oncoceutics, Sanofi Aventis, personal fees from Cavion, INSYS Therapeutics, Monteris, from Novogen, Regeneron Pharmaceuticals, and Tocagen. T.F.C. reports consulting fees from: Roche/Genentech, VBL, Merck, BMS, Pfizer, Agios, Novogen, Boston Biomedical, MedQIA, Tocagen, Cortice Biosciences, Novocure, NewGen, Oxigene, Wellcome Trust, Sunovion Pharmaceuticals, Abbvie, Celgene, Lilly; and reports equity in Notable Labs. B.M.A. is the PI of INSIGhT, and adaptive platform trial supported by Eli Lilly, Celgene, and Puma and is the President and CEO of Global Coalition for Adaptive Research. Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2018",

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doi = "10.1093/neuonc/noy027",

language = "English (US)",

volume = "20",

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number = "8",

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TY - JOUR

T1 - The clinical trials landscape for glioblastoma

T2 - Is it adequate to develop new treatments?

AU - Vanderbeek, Alyssa M.

AU - Rahman, Rifaquat

AU - Fell, Geoffrey

AU - Ventz, Steffen

AU - Chen, Tianqi

AU - Redd, Robert

AU - Parmigiani, Giovanni

AU - Cloughesy, Timothy F.

AU - Wen, Patrick Y.

AU - Trippa, Lorenzo

AU - Alexander, Brian M.

N1 - Funding Information: This work was supported by a Burroughs Wellcome Innovations in Regulatory Science Award. Funding Information: Conflict of interest statement. P.Y.W. reports grants, personal fees and nonfinancial support from Agios and Novartis, nonfinancial support from Angiochem, GlaxoSmithKline, ImmunoCellular Therapeutics, VBI Vaccines, and Karyopharm and personal fees and nonfinancial support from AstraZeneca, Genentech/Roche, and Vascular Biogenics, grants and nonfinancial support from Merck, and nonfinancial support from Oncoceutics, Sanofi Aventis, personal fees from Cavion, INSYS Therapeutics, Monteris, from Novogen, Regeneron Pharmaceuticals, and Tocagen. T.F.C. reports consulting fees from: Roche/Genentech, VBL, Merck, BMS, Pfizer, Agios, Novogen, Boston Biomedical, MedQIA, Tocagen, Cortice Biosciences, Novocure, NewGen, Oxigene, Wellcome Trust, Sunovion Pharmaceuticals, Abbvie, Celgene, Lilly; and reports equity in Notable Labs. B.M.A. is the PI of INSIGhT, and adaptive platform trial supported by Eli Lilly, Celgene, and Puma and is the President and CEO of Global Coalition for Adaptive Research. Publisher Copyright: © 2017 The Author(s).

PY - 2018/7/5

Y1 - 2018/7/5

N2 - Background There have been few treatment advances for patients with glioblastoma (GBM) despite increasing scientific understanding of the disease. While factors such as intrinsic tumor biology and drug delivery are challenges to developing efficacious therapies, it is unclear whether the current clinical trial landscape is optimally evaluating new therapies and biomarkers. Methods We queried ClinicalTrials.gov for interventional clinical trials for patients with GBM initiated between January 2005 and December 2016 and abstracted data regarding phase, status, start and end dates, testing locations, endpoints, experimental interventions, sample size, clinical presentation/indication, and design to better understand the clinical trials landscape. Results Only approximately 8%-11% of patients with newly diagnosed GBM enroll on clinical trials with a similar estimate for all patients with GBM. Trial duration was similar across phases with median time to completion between 3 and 4 years. While 93% of clinical trials were in phases I-II, 26% of the overall clinical trial patient population was enrolled on phase III studies. Of the 8 completed phase III trials, only 1 reported positive results. Although 58% of the phase III trials were supported by phase II data with a similar endpoint, only 25% of these phase II trials were randomized. Conclusions The clinical trials landscape for GBM is characterized by long development times, inadequate dissemination of information, suboptimal go/no-go decision making, and low patient participation.

AB - Background There have been few treatment advances for patients with glioblastoma (GBM) despite increasing scientific understanding of the disease. While factors such as intrinsic tumor biology and drug delivery are challenges to developing efficacious therapies, it is unclear whether the current clinical trial landscape is optimally evaluating new therapies and biomarkers. Methods We queried ClinicalTrials.gov for interventional clinical trials for patients with GBM initiated between January 2005 and December 2016 and abstracted data regarding phase, status, start and end dates, testing locations, endpoints, experimental interventions, sample size, clinical presentation/indication, and design to better understand the clinical trials landscape. Results Only approximately 8%-11% of patients with newly diagnosed GBM enroll on clinical trials with a similar estimate for all patients with GBM. Trial duration was similar across phases with median time to completion between 3 and 4 years. While 93% of clinical trials were in phases I-II, 26% of the overall clinical trial patient population was enrolled on phase III studies. Of the 8 completed phase III trials, only 1 reported positive results. Although 58% of the phase III trials were supported by phase II data with a similar endpoint, only 25% of these phase II trials were randomized. Conclusions The clinical trials landscape for GBM is characterized by long development times, inadequate dissemination of information, suboptimal go/no-go decision making, and low patient participation.

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KW - glioblastoma

KW - regulatory science

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The clinical trials landscape for glioblastoma: Is it adequate to develop new treatments?

Abstract

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