Precision medicine in recurrent glioblastoma: A feasibility trial conducted by the Ivy Foundation Early Phase Clinical Trials Consortium.
Authors: Michael Prados, John G. Kuhn, Howard Colman, Timothy Francis Cloughesy, Susan Marina Chang, Nicholas A. Butowski, John Frederick De Groot, Patrick Y. Wen, Keith L. Ligon, Ingo K. Mellinghoff, Andrew S. Chi, Joanna J Phillips, Annette M Molinaro, Rebecca Halperin, Nhan Tran, Michael E. Berens, John D. Carpten, David W. Craig, Sara A. Byron
Journal: Journal of Clinical Oncology (2016)

Article Tools Central Nervous System Tumors Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2016.34.15_suppl.2031 Journal of Clinical Oncology - published online before print May 20, 2016 Precision medicine in recurrent glioblastoma: A feasibility trial conducted by the Ivy Foundation Early Phase Clinical Trials Consortium. Michael PradosxMichael PradosSearch for articles by this author, John G. KuhnxJohn G. KuhnSearch for articles by this author, Howard ColmanxHoward ColmanSearch for articles by this author, Timothy Francis CloughesyxTimothy Francis CloughesySearch for articles by this author, Susan Marina ChangxSusan Marina ChangSearch for articles by this author, Nicholas A. ButowskixNicholas A. ButowskiSearch for articles by this author, John Frederick De GrootxJohn Frederick De GrootSearch for articles by this author, Patrick Y. WenxPatrick Y. WenSearch for articles by this author, Keith L. LigonxKeith L. LigonSearch for articles by this author, Ingo K. MellinghoffxIngo K. MellinghoffSearch for articles by this author, Andrew S. ChixAndrew S. ChiSearch for articles by this author, Joanna J PhillipsxJoanna J PhillipsSearch for articles by this author, Annette M MolinaroxAnnette M MolinaroSearch for articles by this author, Rebecca HalperinxRebecca HalperinSearch for articles by this author, Nhan TranxNhan TranSearch for articles by this author, Michael E. BerensxMichael E. BerensSearch for articles by this author, John D. CarptenxJohn D. CarptenSearch for articles by this author, David W. CraigxDavid W. CraigSearch for articles by this author, Sara A. ByronxSara A. ByronSearch for articles by this author Show More UC San Francisco, San Francisco, CA; University of Texas Health Science Center San Antonio, San Antonio, TX; Hunstman Cancer Institute of Utah, Salt Lake City, UT; UCLA, Los Angeles, CA; University of California, San Francisco, San Francisco, CA; The University of Texas MD Anderson Cancer Center, Houston, TX; Dana-Farber Cancer Institute, Boston, MA; Memorial Sloan Kettering Cancer Center, New York, NY; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Translational Genomics Research Institute, Phoenix, AZAbstract Disclosures https://doi.org/10.1200/JCO.2016.34.15_suppl.2031 Abstract Abstract2031Background: Pts with recurrent glioblastoma have median survival between 4 to 8 months. "Precision-based" therapies have not been used in this patient population. The goal of this trial was to determine the feasibility to make individualized treatment recommendations within at least 35 days of tumor tissue collection, using whole exome and RNA sequencing based upon those alterations. A sample size of at least 15 patients with sufficient tumor RNA and DNA was used to determine feasibility. Pts. had the option of accepting the recommendation or being treated using other treatment strategies. Adult patients with recurrent glioblastoma who were undergoing tumor resection at the time of relapse as part of their standard of care management were eligible. Methods: Tumor tissue was removed from both enhancing and non-enhancing regions of tumor and characterized by whole exome and RNA sequencing. Molecular profiles were done at Translational Genomics Research Institute (TGen), in a CLIA lab, matching genomic alterations with both cancer positioned and repositioned drugs. Up to 4 agents could be selected by a Molecular Tumor Board convened after each case to discuss prior patient treatment history, molecular alterations, and drug options. The treatment recommendation was based upon alterations from the enhancing tumor region. Non-enhancing tumor profiles, patient-derived xenografts, and circulating tumor DNA samples (obtained prior to and following surgery, and every 8 weeks) were used for correlative endpoints. Results: 20 patients were enrolled, and 16 had sufficient tumor content to profile. There were 3 feasibility failures (1 pt. took > 35 days to profile; 2 pts. did not have sufficient RNA content). Of the 16 eligible cases, the average time from surgery to Tumor Board was 27 days, with an average of 3.4 drugs recommended (range 1-4) including at least 1 repositioned agent in 13 cases. 7 pts accepted the Tumor Board recommendation. Molecular findings will be presented. Conclusions: It is possible to obtain useable genomic information at the time of relapse, and make treatment recommendations within weeks. Efficacy studies are being planned using this strategy. Clinical trial information: NCT02060890.© 2016 by American Society of Clinical Oncology