Safety and feasibility of tumor treating fields initiated before and during radiotherapy for newly diagnosed glioblastoma: results from the arm a feasibility cohort of a Phase I/II Trial (PriCoTTF)

Abstract Background Tumor Treating Fields improve survival when started after chemoradiotherapy in newly diagnosed glioblastoma, but the safety and feasibility of initiating treatment before and during radiotherapy remain uncertain. Methods PriCoTTF is a prospective, open-label, nonrandomized, multicenter phase I/II trial. Arm A enrolled adults aged 18 to 70 years with newly diagnosed IDH-wildtype glioblastoma or gliosarcoma, Karnofsky Performance Status of at least 60, and planned focal radiotherapy to 60 Gy in 30 fractions. TTFields at 200 kHz were initiated 2 to 4 weeks after surgery and 1 to 2 weeks before radiotherapy. The primary endpoint was protocol-defined treatment-limiting toxicity from TTFields initiation through 4 weeks after radiotherapy. Results Twenty evaluable patients comprised the Arm A feasibility cohort. No protocol-defined treatment-limiting toxicities occurred (0 of 20 patients; exact 95% CI, 0.0%-16.8%). Grade 3 or higher adverse events occurred in 12 patients (60%), predominantly hematologic toxicity attributable to chemoradiotherapy; lymphopenia occurred in 6 patients (30%). Median usage through visit 4 was 76.5%, and median time to first attainment of at least 75% daily use was 2 days. Median progression-free survival was 6.9 months (95% CI, 2.7–14.0), and median overall survival was 18.0 months (95% CI, 12.1–19.9). Conclusions Initiation of TTFields before and during radiotherapy was feasible and was not associated with protocol-defined treatment-limiting toxicity in the Arm A cohort. Because the TLT definition was narrow and efficacy analyses were exploratory and exposure-conditioned, these findings should be interpreted as feasibility data rather than evidence of improved tumor control or survival. The results support randomized evaluation of earlier TTFields integration in newly diagnosed glioblastoma. Trial registration German Clinical Trials Register DRKS00016667, registered 26 February 2019.