355TiP - METIS: A phase III study of radiosurgery with TTFields for 1-10 brain metastases from NSCLC

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Central Nervous System Malignancies
Surgery and/or Radiotherapy of Cancer
Presenter Minesh Mehta
Citation Annals of Oncology (2016) 27 (6): 103-113. 10.1093/annonc/mdw367
Authors M.P. Mehta1, V. Gondi2, P.D. Brown3
  • 1Radiation Oncology, University of Maryland School of Medicine, 21201-1559 - Baltimore/US
  • 2Radiation Oncology, Northwestern Medicine Cancer Center, Chicago/US
  • 3Radiation Oncology, MD Anderson Cancer Center, Houston/US

Abstract

Background

Tumor Treating Fields (TTFields) are a novel, non-invasive regional anti-mitotic treatment modality, based on low intensity alternating electric fields. Efficacy of TTFields in non-small cell lung cancer (NSCLC) has been demonstrated in multiple in vitro and in vivo models, and in a phase I/II clinical study. TTFields treatment to the brain was shown to be safe and effective in glioblastoma patients.

Trial design

270 patients with 1-10 brain metastases (BM) from NSCLC will be randomized in a ratio of 1:1 to receive stereotactic radio surgery (SRS) followed by either TTFields or supportive care alone. Patients are followed-up every two months until 2nd cerebral progression. Patients in the control arm may cross over to receive TTFields at the time of 1st cerebral progression. Objectives: To test the efficacy, safety and neurocognitive outcomes of TTFields in this patient population. Endpoints: Time to 1st cerebral progression (primary); time to neurocognitive failure based on the following tests: HVLT, COWAT and TMT; overall survival; radiological response rate; quality of life; adverse events severity and frequency (secondary). Treatment: Continuous TTFields at 150 kHz will be applied to the brain within 7 days of SRS. The treatment system is a portable medical device allowing normal daily life activities. The device delivers TTFields to the brain using 4 Transducer Arrays, which may be covered by a wig or a hat for cosmetic reasons. Patients will receive the best standard of care for their systemic disease. Statistical Considerations: This is a prospective, randomized, multicenter study for 270 patients. The trial is designed to detect an increase in the time to cerebral progression from 7.7 to 13.4 months (hazard ratio 0.57). This sample size assessment takes into consideration a competing risk (death prior to cerebral progression) of 0.08252 per month in both treatment arms. The competing risk is based on a predicted median overall survival of 8.4 months mainly due to systemic disease progression. The trial has 80% power at a two sided alpha of 0.05. The sample size was calculated using a log-rank test (based on Lakatos 1988 and 2002).

Clinical trial identification

Legal entity responsible for the study

FDA

Funding

Novocure Ltd.

Disclosure

All authors have declared no conflicts of interest.