Background: We will initiate (March 2020) a randomized, comparative, multi-center, investigator-initiated, interventional, phase 2 trial (NCT04223999) testing the efficacy of a potentially new treatment modality for recurrent glioblastoma (GBM). The new treatment modality combines individualized targeted skull remodeling surgery (SR-surgery) with Tumor Treating Fields (TTFields) and best practice medical oncological therapy. The aim of SR-surgery is to enhance the electric field in the tumor region, by removing bone with burrholes. Preclinical research indicate that this modality provides a marked and focal enhancement (~100%) of TTFields. We concluded (April 2019) a phase 1 safety/feasibility trial indicating improved overall survival without additional toxicity from the intervention. The following randomized, comparative phase 2 trial aims to validate superior efficacy of the intervention.
Method: The trial is designed as a comparative, 1:1 randomized, minimax two-stage phase 2 with an expected 70 patients to a maximum sample size of 84 patients. After 12-months follow-up of the first 52 patients an interim futility analysis will be performed. The two trial arms will consist of either a) TTFields, best practice oncological treatment (control arm) or b) SR-surgery, TTFields and best practice oncology (interventional arm).Major eligibility criteria include age ≥ 18 years, supratentorial GBM, Karnofsky performance score (KPS) ≥ 70, focal tumor, and lack of uncontrollable epilepsy or significant co-morbidity. Study design aims to detect a 20% increase in the overall survival rate 12 months (OS12) assuming OS12 = 40% in the control group and OS12= 60% in the intervention group. Secondary endpoints include hazard rate ratio of overall survival and progression-free survival, objective response rate, quality of life, KPS, steroid dose, and toxicity. Patient follow-up is until death or 36 months (trial duration). Expected average for follow-up is 18 months. Every 3. month there will be an assessment of toxicity, response and QoL. Endpoint data will be collected at the end of the trial, occurrence of suspected unexpected serious adverse reactions (SUSARs) or unacceptable serious adverse events (SAEs), withdrawal of consent, or loss-to-follow-up.
Citation Format: Nikola Mikic, Anders R. Korshøj. Optimizing Tumor Treating Fields therapy for recurrent glioblastoma with targeted and individualized skull remodeling surgery. A multi-center randomized phase 2 trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT184.