A genomically-tailored multi-agent precision medicine clinical trial for adults with recurrent glioblastoma
We conducted a single arm, non-randomized open-label phase 1 clinical trial to assess the feasibility, safety, and efficacy of a genomically-tailored multi-agent regimen in 30 adults with surgically-treated recurrent glioblastoma (ClinicalTrials.gov ID NCT03681028). Adults with IDH-wildtype glioblastoma (n=29) or grade 4 IDH-mutant astrocytoma (n=1) were consented and underwent clinically indicated surgery for recurrent disease. Comprehensive genomic profiling was performed on the recurrent tumors, and results for each patient were discussed at an individualized molecular tumor board to determine a personalized treatment regimen combining up to 4 FDA-approved drugs, including one cytotoxic agent as backbone. Capture-based next-generation DNA sequencing was performed on the recurrent glioblastoma tumor specimens from the 30 patients, along with a paired constitutional DNA sample from buccal swab or peripheral blood, in a CLIA-certified laboratory using the UCSF500 NGS panel as previously described that targets all coding exons of 529 cancer-related genes, select introns and upstream regulatory regions of 73 genes to enable detection of structural variants including gene fusions, and DNA segments at regular intervals along each chromosome to enable genome-wide copy number and zygosity analysis. For a subset of patients (n=9), a subsequent surgical resection was performed upon disease progression during the precision medicine clinical trial regimen. Genomic profiling using the identical platform and methodology was performed on these post-clinical trial treatment tumor specimens.