OPEN-LABEL PHASE 1 CLINICAL TRIAL TESTING PERSONALIZED AND TARGETED INTERVENTION WITH SKULL REMODELLING SURGERY TO MAXIMIZE LEVELS OF TTFIELDS INTENSITY FOR HIGHER TREATMENT BENEFIT - THE OPTIMAL TTF STUDY

We present an ongoing open label phase 1 investigator-sponsored trial (NCT02893137) testing safety/efficacy of a novel therapeutic concept for recurrent glioblastoma (GBM). The intervention combines best choice chemotherapy with tumor treating fields (TTFields) and personalized targeted skull remodeling surgery. The objective of skull remodeling surgery is to create paths, which facilitate electric current flow through into the region of pathology. This may involve formation of strategically placed minor craniectomies or burr holes and thinning of the skull. Finite element (FE) calculations indicate that skull remodeling surgery provides a marked and focal enhancement (~100%) of TTFields intensity without significantly compromising patient safety. Patient accrual began Dec 2016. As of June 2017 seven patients have been screened and six out of fifteen patients enrolled. Major eligibility criteria include age > 18 years, first recurrence supratentorial GBM, Karnofsky performance score (KPS) > 60, focal tumor < 2 cm to cortical surface, lack of uncontrollable epilepsy, and lack of significant co-morbidity. Upon inclusion, personalized FE-calculations are performed to validate TTFields enhancement > 25% due by skull remodeling surgery. The primary endpoint is toxicity assessed by CTCAEv4.0. Secondary endpoints include overall survival, progression free survival (PFS), PFS at six months (PFS6), objective response rate (RANO), quality of life (EORTC QLQ-C30 and BN20), KPS, and steroid dose. Follow-up is 18 months and includes regular toxicity assessment (6 week intervals) as well as quality of life and response assessments (3 month intervals). Patients are censored at the end of scheduled follow-up, occurrence of serious or unacceptable adverse events, withdrawal of consent, or loss to follow-up. Interim analysis will be performed upon censoring of the first five patients. The tested concept holds promising potential for improving TTFields outcome by enhancing field intensity in the tumor. The trial will hopefully lay the foundation for future efficacy investigation.