Alyssa M Vanderbeek1,2, Rifaquat Rahman1,2, Geoffrey Fell3,4,2, Steffen Ventz2,5, Tianqi Chen3,4,2, Robert Redd3,4,2, Giovanni Parmigiani3,4,2, Timothy F Cloughesy6, Patrick Y Wen7, Lorenzo Trippa3,4,2, Brian M Alexander1,7,2. 1. Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts. 2. Dana-Farber Program in Regulatory Science, Harvard Medical School, Boston, Massachusetts. 3. Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 4. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 5. Department of Computer Science and Statistics, University of Rhode Island, Kingston, Rhode Island. 6. University of California Los Angeles, Neuro-Oncology Program. 7. Center for Neuro-Oncology, Harvard Medical School, Boston, Massachusetts.
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.
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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