PATH-27. IDENTIFYING THE GENETIC SIGNATURE OF RESPONSE IN A PHASE II STUDY OF TUMOR TREATING FIELDS IN RECURRENT GLIOBLASTOMA
Autor: | Valerie Greene, Gregory J. A. Murad, Sonisha Warren, William A. Friedman, Maryam Rahman, Anthony T. Yachnis, David Tran, Ashley Ghiaseddin, Steven N. Roper, Anne Allen |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Cancer Research Bevacizumab business.industry Recurrent glioblastoma Complete remission Phases of clinical research medicine.disease 03 medical and health sciences Genetic signature Abstracts 030104 developmental biology 0302 clinical medicine Oncology 030220 oncology & carcinogenesis Path (graph theory) Cancer research Medicine Neurology (clinical) business Diagnostic radiologic examination Glioblastoma medicine.drug |
Popis: | Prognosis of relapsed glioblastoma (GBM) is dismal and current treatment fails to provide prolonged survival. Small subsets of patients respond well to some novel therapeutics probably due to the genetic variations of tumors and patients. In the Phase 3 EF-11 recurrent GBM trial, a small subset of patients derived significant benefit from TTFields alone. This proof-of-concept trial [NCT01954576] will study adult patients with relapsed GBM treated with TTFields by genetic analysis of primary and recurrent tumors. Post-hoc correlations will be used between clinical response, mutational analyses and quantitative gene expression to define genomic signatures of response. Whole exome and RNA sequencing will be used to identify genomic signature of responders to TTFields. Fifteen patients with bevacizumab-naïve recurrent GBM and 15 patients with bevacizumab-refractory GBM will be treated with TTFields for 6 and 4 months respectively. Patients will undergo standard brain MRI scans without and with gadolinium contrast and perfusion imaging every 8 weeks. Tissue from the primary tumor at recurrence will be genetically analyzed. Genomic DNA (gDNA) will be extracted from patients tumor and blood samples. Purified gDNA fragments will be used for Illumina sequencing library construction. Certain germ-line variants may contribute to gliomagenesis and be associated with somatic mutations within the tumor and subtypes of GBM more or less sensitive to TTFields. Analyses will be conducted on all patients: bevacizumab-naïve and bevacizumab-refractory GBM separately, and patients with objective radiographic response (complete response + partial response (CR + PR) and stable disease (SD) separately. With 50% bevacizumab-refractory GBM patients, response rate will be significantly higher than the baseline rate of 14%. Using an Exact test with type I error of 0.05 and 80% power, the estimated sample sizes will detect a statistical difference on response rate in the TTFields group compared to historical controls. To-date 4 patients have been enrolled. |
Databáze: | OpenAIRE |
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