PHASE-III TRIAL OF STANDARD CHEMOTHERAPY VS. CHEMOTHERAPY GUIDED BY CANCER STEM CELL TEST IN RECURRENT GLIOBLASTOMA (NCT03632135)

Abstract Stupp treatment protocol for patients with glioblastoma (GBM) has improved the median overall survival to 14.6 months. However, no investigations have defined effective strategies against recurrence and the prognosis of recurrent GBM patients remains poor. Personalized medicine with assay-guided treatment targeting chemotherapy resistant cancer stem cells (CSCs) alongside the bulk tumor cells is a new paradigm in cancer treatment that may result in improved patient’s outcome. We are using ChemoID, a CLIA and CAP certified CSC cytotoxicity assay for predicting response to chemotherapeutic agents. Our prospective analysis of 61 GBM patients demonstrated that ChemoID-guided treatment significantly improved tumor response. For every 5% increase in cell kill of CSCs by assay-guided chemotherapy, 12-month patient response (non-recurrence of cancer) increased 2.5-fold, OR=2.3 (p=0.01). We also found that median recurrence time was 20-months versus 3-months for patients with a positive (>40% cell kill) CSC test versus negative, whereas median recurrence time was 13-months versus 4-months for patients with a positive (>55% cell kill) bulk test versus negative. We are conducting a multi-institutional phase-III clinical trial (NCT03632135) to determine the clinical validity of the ChemoID assay as a predictor of clinical response in recurrent GBM. The study has been designed as a parallel group controlled clinical trial and the participants are randomized to either standard of care chemotherapy chosen by the physician or ChemoID-guided therapy. Response to therapy will be measured by MRI imaging using RANO criteria. Primary endpoint of median overall survival (OS) and secondary endpoints of OS at 6, 9, and 12 months, median progression free survival (PFS), PFS at 4, 6, 9, and 12 months, objective tumor response, time to recurrence, and quality of life will be measured. Trial is open and currently 22 subjects have been enrolled. Interim analysis of the trial will be conducted in approximately 12 months.