An Analysis of Interventional Clinical Trials and Trends in Potential Glioblastoma Therapeutics
DOI:
https://doi.org/10.47611/jsrhs.v12i3.4500Keywords:
Clinical trial, meta-analysis, Glioblastoma, Cancer, Tumor, Clinical TrialsAbstract
Glioblastoma Multiforme (GBM), an aggressive malignant tumor of the central nervous system, carries a poor prognosis. This research aimed to analyze the current and future trends of interventional GBM clinical trials. Analyzed trials met the following eligibility criteria: registration between January 1st, 2012, and July 19, 2022, of interventional study type, in trial phases II-IV, and were either completed, recruiting, or active. Of 1,728 GBM-related trials, 336 were eligible. A majority of trials were of open-label masking (89.58%, n=301), academia-sponsored (44.94%, n=151), and systemic interventions (87.20%, n=293). Despite an increasing trend in the number of trials initiated, other findings provided a basis for concern: negligible focus on localized interventions, minimal funding by industry, and widespread use of open-label maskingof funding by industry and minimal trials examining localized therapies hinders the availability of interventions and the improvement of treatment techniques, respectively. Likewise, open-label masking is not the standard, nor is the use supported in clinical trial studies, as it does not eliminate placebo responses. These conclusions are the basis of concerns and areas of improvement in the GBM clinical trial landscape.
Downloads
References or Bibliography
Ameratunga, M., Pavlakis, N., Wheeler, H., Grant, R., Simes, J., & Khasraw, M. (2018). Anti-angiogenic therapy for high-grade glioma. The Cochrane Database of Systematic Reviews, 11(11). https://doi.org/10.1002/14651858.CD008218.PUB4
Ballou, S., Kaptchuk, T. J., Hirsch, W., Nee, J., Iturrino, J., Hall, K. T., Kelley, J. M., Cheng, V., Kirsch, I., Jacobson, E., Conboy, L., Lembo, A., & Davis, R. B. (2017). Open-label versus double-blind placebo treatment in irritable bowel syndrome: Study protocol for a randomized controlled trial. Trials, 18(1), 1–15. https://doi.org/10.1186/S13063-017-1964-X/TABLES/3
Barone, D. G., Lawrie, T. A., & Hart, M. G. (2014). Image guided surgery for the resection of brain tumours. The Cochrane Database of Systematic Reviews, 2014(1). https://doi.org/10.1002/14651858.CD009685.PUB2
Batash, R., Asna, N., Schaffer, P., Francis, N., & Schaffer, M. (2017). Glioblastoma Multiforme, Diagnosis and Treatment; Recent Literature Review. Current Medicinal Chemistry, 24(27). https://doi.org/10.2174/0929867324666170516123206
Behnan, J., Finocchiaro, G., & Hanna, G. (2019). The landscape of the mesenchymal signature in brain tumours. Brain : A Journal of Neurology, 142(4), 847–866. https://doi.org/10.1093/BRAIN/AWZ044
Bunevicius, A., & Sheehan, J. P. (2021). Radiosurgery for Glioblastoma. Neurosurgery Clinics of North America, 32(1), 117–128. https://doi.org/10.1016/J.NEC.2020.08.007
Chakravarti, A., Erkkinen, M. G., Nestler, U., Stupp, R., Mehta, M., Aldape, K., Gilbert, M. R., Black, P. M. L., & Loeffler, J. S. (2006). Temozolomide-mediated radiation enhancement in glioblastoma: a report on underlying mechanisms. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 12(15), 4738–4746. https://doi.org/10.1158/1078-0432.CCR-06-0596
Cihoric, N., Tsikkinis, A., Minniti, G., Lagerwaard, F. J., Herrlinger, U., Mathier, E., Soldatovic, I., Jeremic, B., Ghadjar, P., Elicin, O., Lössl, K., Aebersold, D. M., Belka, C., Herrmann, E., & Niyazi, M. (2017). Current status and perspectives of interventional clinical trials for glioblastoma - analysis of ClinicalTrials.gov. Radiation Oncology, 12(1), 1–12. https://doi.org/10.1186/S13014-016-0740-5/FIGURES/4
Daneman, R., & Prat, A. (2015). The blood-brain barrier. Cold Spring Harbor Perspectives in Biology, 7(1). https://doi.org/10.1101/CSHPERSPECT.A020412
Davis, M. E. (2016). Glioblastoma: Overview of disease and treatment. Clinical Journal of Oncology Nursing, 20(5), 1–8. https://doi.org/10.1188/16.CJON.S1.2-8
del Álamo, M., Bührer, C., Fisher, D., Griese, M., Lingor, P., Palladini, G., Sireau, N., Hivert, V., Sangiorgi, L., Guillot, F., Halftermeyer, J., Soucková, L., Nosková, K., & Demlová, R. (2022). Identifying obstacles hindering the conduct of academic-sponsored trials for drug repurposing on rare-diseases: an analysis of six use cases. Trials, 23(1), 1–10. https://doi.org/10.1186/S13063-022-06713-Y/TABLES/3
Delgado-Martín, B., & Medina, M. Á. (2020). Advances in the Knowledge of the Molecular Biology of Glioblastoma and Its Impact in Patient Diagnosis, Stratification, and Treatment. Advanced Science, 7(9). https://doi.org/10.1002/ADVS.201902971
Ellingson, B. M., Abrey, L. E., Nelson, S. J., Kaufmann, T. J., Garcia, J., Chinot, O., Saran, F., Nishikawa, R., Henriksson, R., Mason, W. P., Wick, W., Butowski, N., Ligon, K. L., Gerstner, E. R., Colman, H., De Groot, J., Chang, S., Mellinghoff, I., Young, R. J., … Cloughesy, T. F. (2018). Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma. Neuro-Oncology, 20(9), 1240–1250. https://doi.org/10.1093/NEUONC/NOY053
Fabbro-Peray, P., Zouaoui, S., Darlix, A., Fabbro, M., Pallud, J., Rigau, V., Mathieu-Daude, H., Bessaoud, F., Bauchet, F., Riondel, A., Sorbets, E., Charissoux, M., Amelot, A., Mandonnet, E., Figarella-Branger, D., Duffau, H., Tretarre, B., Taillandier, L., & Bauchet, L. (2019). Association of patterns of care, prognostic factors, and use of radiotherapy-temozolomide therapy with survival in patients with newly diagnosed glioblastoma: a French national population-based study. Journal of Neuro-Oncology, 142(1), 91–101. https://doi.org/10.1007/S11060-018-03065-Z
Fisher, J. P., & Adamson, D. C. (2021). Current FDA-Approved Therapies for High-Grade Malignant Gliomas. Biomedicines, 9(3). https://doi.org/10.3390/BIOMEDICINES9030324
Hanif, F., Muzaffar, K., Perveen, K., Malhi, S. M., & Simjee, S. U. (2017). Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment. Asian Pacific Journal of Cancer Prevention : APJCP, 18(1), 3. https://doi.org/10.22034/APJCP.2017.18.1.3
Huang, B., Zhang, H., Gu, L., Ye, B., Jian, Z., Stary, C., & Xiong, X. (2017). Advances in Immunotherapy for Glioblastoma Multiforme. https://doi.org/10.1155/2017/3597613
Jena, B., Dotti, G., & Cooper, L. J. N. (2010). Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood, 116(7), 1035–1044. https://doi.org/10.1182/BLOOD-2010-01-043737
Lin, D., Wang, M., Chen, Y., Gong, J., Chen, L., Shi, X., Lan, F., Chen, Z., Xiong, T., Sun, H., & Wan, S. (2021). Trends in Intracranial Glioma Incidence and Mortality in the United States, 1975-2018. Frontiers in Oncology, 11, 4479. https://doi.org/10.3389/FONC.2021.748061/BIBTEX
Louis, D. N., Perry, A., Wesseling, P., Brat, D. J., Cree, I. A., Figarella-Branger, D., Hawkins, C., Ng, H. K., Pfister, S. M., Reifenberger, G., Soffietti, R., Von Deimling, A., & Ellison, D. W. (2021). The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-Oncology, 23(8), 1231. https://doi.org/10.1093/NEUONC/NOAB106
Minniti, G., Lombardi, G., & Paolini, S. (2019). Glioblastoma in Elderly Patients: Current Management and Future Perspectives. Cancers, 11(3). https://doi.org/10.3390/CANCERS11030336
Ostrom, Q. T., Cioffi, G., Waite, K., Kruchko, C., & Barnholtz-Sloan, J. S. (2021). CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018. Neuro-Oncology, 23(12 Suppl 2), III1–III105. https://doi.org/10.1093/NEUONC/NOAB200
Ramón y Cajal, S., Sesé, M., Capdevila, C., Aasen, T., De Mattos-Arruda, L., Diaz-Cano, S. J., Hernández-Losa, J., & Castellví, J. (2020). Clinical implications of intratumor heterogeneity: challenges and opportunities. Journal of Molecular Medicine (Berlin, Germany), 98(2), 161–177. https://doi.org/10.1007/S00109-020-01874-2
Razavi, S. M., Lee, K. E., Jin, B. E., Aujla, P. S., Gholamin, S., & Li, G. (2016). Immune Evasion Strategies of Glioblastoma. Frontiers in Surgery, 3. https://doi.org/10.3389/FSURG.2016.00011
Robinson, D. R., Wu, Y. M., & Lin, S. F. (2000). The protein tyrosine kinase family of the human genome. Oncogene, 19(49), 5548–5557. https://doi.org/10.1038/SJ.ONC.1203957
Sanai, N., & Berger, M. S. (2008). Glioma extent of resection and its impact on patient outcome. Neurosurgery, 62(4), 753–764. https://doi.org/10.1227/01.NEU.0000318159.21731.CF
Shah, H. A., Mishra, A., Gouzoulis, M. J., Ben-Shalom, N., & D’Amico, R. S. (2022). Analysis of factors leading to early termination in glioblastoma-related clinical trials. Journal of Neuro-Oncology, 158(3), 489. https://doi.org/10.1007/S11060-022-04039-Y
Shergalis, A., Bankhead, A., Luesakul, U., Muangsin, N., & Neamati, N. (2018). Current challenges and opportunities in treating glioblastomas. Pharmacological Reviews, 70(3), 412–445. https://doi.org/10.1124/PR.117.014944
Stummer, W., Reulen, H. J., Meinel, T., Pichlmeier, U., Schumacher, W., Tonn, J. C., Rohde, V., Oppel, F., Turowski, B., Woiciechowsky, C., Franz, K., Pietsch, T., Oppel, F., Brune, A., Lanksch, W., Woiciechowsky, C., Brock, M., Vesper, J., Goetz, C., … Stummer, W. (2008). Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery, 62(3), 564–574. https://doi.org/10.1227/01.NEU.0000317304.31579.17
Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., Curschmann, J., Janzer, R. C., Ludwin, S. K., Gorlia, T., Allgeier, A., Lacombe, D., Cairncross, J. G., Eisenhauer, E., & Mirimanoff, R. O. (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. The New England Journal of Medicine, 352(10), 987–996. https://doi.org/10.1056/NEJMOA043330
Tamimi, A. F., & Juweid, M. (2017). Epidemiology and Outcome of Glioblastoma. Glioblastoma, 143–153. https://doi.org/10.15586/CODON.GLIOBLASTOMA.2017.CH8
Thust, S. C., van den Bent, M. J., & Smits, M. (2018). Pseudoprogression of brain tumors. Journal of Magnetic Resonance Imaging, 48(3), 571. https://doi.org/10.1002/JMRI.26171
Verhaak, R. G. W., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., Miller, C. R., Ding, L., Golub, T., Mesirov, J. P., Alexe, G., Lawrence, M., O’Kelly, M., Tamayo, P., Weir, B. A., Gabriel, S., Winckler, W., Gupta, S., Jakkula, L., … Hayes, D. N. (2010). Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell, 17(1), 98–110. https://doi.org/10.1016/J.CCR.2009.12.020
Wang, X., Prager, B. C., Wu, Q., Kim, L. J. Y., Gimple, R. C., Shi, Y., Yang, K., Morton, A. R., Zhou, W., Zhu, Z., Obara, E. A. A., Miller, T. E., Song, A., Lai, S., Hubert, C. G., Jin, X., Huang, Z., Fang, X., Dixit, D., … Rich, J. N. (2018). Reciprocal Signaling between Glioblastoma Stem Cells and Differentiated Tumor Cells Promotes Malignant Progression. Cell Stem Cell, 22(4), 514-528.e5. https://doi.org/10.1016/J.STEM.2018.03.011
Weller, M. (2013). Assessing the MGMT status in glioblastoma: one step forward, two steps back? Neuro-Oncology, 15(3), 253–254. https://doi.org/10.1093/NEUONC/NOT014
Wu, W., Klockow, J. L., Zhang, M., Lafortune, F., Chang, E., Jin, L., Wu, Y., & Daldrup-Link, H. E. (2021a). Glioblastoma Multiforme (GBM): An overview of current therapies and mechanisms of resistance HHS Public Access. Pharmacol Res, 171, 105780. https://doi.org/10.1016/j.phrs.2021.105780
Wu, W., Klockow, J. L., Zhang, M., Lafortune, F., Chang, E., Jin, L., Wu, Y., & Daldrup-Link, H. E. (2021b). Glioblastoma Multiforme (GBM): An overview of current therapies and mechanisms of resistance HHS Public Access. Pharmacol Res, 171, 105780. https://doi.org/10.1016/j.phrs.2021.105780
Xu, S., Tang, L., Li, X., Fan, F., & Liu, Z. (2020). Immunotherapy for glioma: Current management and future application. Cancer Letters, 476, 1–12. https://doi.org/10.1016/J.CANLET.2020.02.002
Published
How to Cite
Issue
Section
Copyright (c) 2023 Ananya Uddanti
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Copyright holder(s) granted JSR a perpetual, non-exclusive license to distriute & display this article.