Phase III trial of tumor-treating fields (TTFields) together with temozolomide compared with temozolomide (TMZ) alone in patients with newly diagnosed glioblastoma multiforme (NCT00916409).

TPS2106 Background: TTFields therapy is a novel, non-invasive, anti-mitotic treatment, inhibiting tumor growth by interfering with the metaphase to anaphase transition during mitosis (Lee et al., 2011). TTF therapy was recently approved by the FDA for recurrent GBM following a prospective, randomized trial. Preclinical studies have shown TTFields and TMZ to have an additive inhibitory effect on glioma cell proliferation. The design for the current study was supported by results from a pilot study with TTFields therapy and TMZ in patients with newly diagnosed GBM demonstrating favorable safety, tolerability and promising efficacy (Kirson et al., 2009). Methods: The hypothesis of the current study is that the addition of TTFields therapy to maintenance TMZ will increase progression free survival (PFS) of newly diagnosed GBM patients. Secondary endpoints include overall survival (OS), radiological response, quality of life and safety. Eligible patients will be randomized (2:1) to continuous TTFields therapy (200 kHz) in combination with maintenance TMZ versus maintenance TMZ alone. Maintenance TMZ will be administered as per the Stupp Protocol for 6 courses (Stupp et al., 2005). TTFields therapy may be administered for up to 24 months. Patients will be stratified based on: extent of resection and MGMT methylation status. Eligibility criteria include: pathological diagnosis of GBM; Karnofsky ≥ 70; previous chemoradiotherapy per Stupp Protocol; no progressive disease at baseline. Patients with infratentorial tumor or implanted electronic devices are excluded. The sample size of 700 patients will have 80% power to detect a 2 month (9 vs 7 months) improvement in PFS using log-rank test with an overall 5% 2-sided type I error. The trial is also powered to detect a 4.5 month increase in median OS in NovoTTF-100A/TMZ patients. Patients will be followed clinically monthly and with bimonthly MRI to assess tumor progression and additional endpoints. 221 patients have been enrolled at the time of abstract submission. The DMC last reviewed the trial in October 2010 and recommended that the trial continue as designed.