| Popis: |
BACKGROUND We present an upcoming(Sep. 2020) randomized, comparative, multi-center, investigator-initiated, interventional, phase 2 trial testing the efficacy of a novel therapeutic concept for recurrent glioblastoma(GBM). The intervention combines personalized targeted skull remodeling surgery(SR-surgery) with Tumor Treating Fields(TTFields) and best practice medical oncological therapy. SR-surgery involves strategically placed burr holes to strengthen the electric field in the tumor region. Preclinical studies indicate that SR-surgery provides a marked and focal enhancement(~100%) of TTFields. We recently concluded a phase 1 safety/feasibility study indicating promising clinical efficacy and no clinically significant toxicity related to the intervention. This subsequent randomized, comparative phase 2 trial aims to validate superior efficacy of the treatment. METHOD We will utilize a comparative, 1:1 randomized, minimax two-stage phase 2 design with an expected sample size of 70 patients, interim futility analysis at 1-yr follow-up of the first 52 patients and a maximum sample size of 84 patients. Patients will receive either 1)TTFields and best practice medical oncological treatment(control arm) or 2) SR-surgery plus TTFields and best practice medical oncological treatment (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. The study is designed 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 ratio of overall survival and progression-free survival, objective response rate, QoL, KPS, steroid dose, and toxicity. Patients will be followed for the whole trial period(36 months). The average expected follow-up is 18 months and includes regular 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. |
