Neurooncology clinical trial design for targeted therapies: Lessons learned from the North American Brain Tumor Consortium Journal Article

   


Authors: Chang, S. M.; Lamborn, K. R.; Kuhn, J. G.; Yung, W. K. A.; Gilbert, M. R.; Wen, P. Y.; Fine, H. A.; Mehta, M. P.; Deangelis, L. M.; Lieberman, F. S.; Cloughesy, T. F.; Robins, H. I.; Abrey, L. E.; Prados, M. D.
Article Title: Neurooncology clinical trial design for targeted therapies: Lessons learned from the North American Brain Tumor Consortium
Abstract: The North American Brain Tumor Consortium (NABTC) is a multi-institutional consortium with the primary objective of evaluating novel therapeutic strategies through early phase clinical trials. The NABTC has made substantial changes to the design and methodology of its trials since its inception in 1994. These changes reflect developments in technology, new types of therapies, and advances in our understanding of tumor biology and biological markers. We identify the challenges of early clinical assessment of therapeutic agents by reviewing the clinical trial effort of the NABTC and the evolution of the protocol template used to design trials. To better prioritize effort and allocation of patient resources and funding, we propose an integrated clinical trial design for the early assessment of efficacy of targeted therapies in neurooncology. This design would mandate tissue acquisition prior to therapeutic intervention with the drug, allowing prospective evaluation of its effects. It would also include a combined phase 0/I pharmacoki- netic study to determine the safety and biologically optimal dose of the agent and to verify successful modulation of the target prior to initiating a larger, phase II efficacy study. Copyright 2008 by the Society for Neuro-Oncology.
Keywords: treatment outcome; overall survival; thalidomide; clinical feature; clinical trial; review; sorafenib; angiogenesis inhibitor; bevacizumab; cytotoxic agent; erlotinib; dose response; drug efficacy; hypertension; solid tumor; paclitaxel; cancer patient; research design; rituximab; temozolomide; recurrent cancer; brain tumor; methodology; brain neoplasms; imatinib; carboplatin; unindexed drug; progression free survival; phase 2 clinical trial; practice guideline; antineoplastic activity; carmustine; central nervous system tumor; irinotecan; temsirolimus; standard; phenobarbital; thromboembolism; glioblastoma; gefitinib; tipifarnib; aflibercept; cediranib; pazopanib; medical society; vorinostat; clinical research; drug clearance; meningioma; maximum tolerated dose; phase 1 clinical trial; clinical trials, phase i as topic; clinical trials, phase ii as topic; retinoic acid; brain hemorrhage; proteinuria; lapatinib; phenytoin; clinical trials; thymidine; cilengitide; carbamazepine; fenretinide; north american brain tumor consortium, targeted therapies; phenylacetic acid
Journal Title: Neuro-Oncology
Volume: 10
Issue: 4
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2008-08-01
Start Page: 631
End Page: 642
Language: English
DOI: 10.1215/15228517-2008-021
PUBMED: 18559968
PROVIDER: scopus
PMCID: PMC2666238
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-54049107406&partnerID=40&md5=dd3145e527356275c61a7161654155d0
Notes: --- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "CODEN: NEURJ" - "Source: Scopus"
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MSK Authors
  1. Lisa De Angelis
    576 De Angelis
  2. Lauren E Abrey
    278 Abrey
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