Study protocol for OptimalTTF-2: enhancing Tumor Treating Fields with skull remodeling surgery for first recurrence glioblastoma: a phase 2, multi-center, randomized, prospective, interventional trial.

BACKGROUND: OptimalTTF-2 is a randomized, comparative, multi-center, investigator-initiated, interventional study aiming to test skull remodeling surgery in combination with Tumor Treating Fields therapy (TTFields) and best physicians choice medical oncological therapy for first recurrence in glioblastoma patients. OptimalTTF-2 is a phase 2 trial initiated in November 2020. Skull remodeling surgery consists of five burrholes, each 15 mm in diameter, directly over the tumor resection cavity. Preclinical research indicates that this procedure enhances the effect of Tumor Treating Fields considerably. We recently concluded a phase 1 safety/feasibility trial that indicated improved overall survival and no additional toxicity. This phase 2 trial aims to validate the efficacy of the proposed intervention. METHODS: 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 therapy combined with best physicians choice oncological treatment (control arm) or b) skull remodeling surgery, TTFields therapy and best practice oncology (interventional arm). Major eligibility criteria include age ≥ 18 years, 1st recurrence of supratentorial glioblastoma, Karnofsky performance score ≥ 70, focal tumor, and lack of significant co-morbidity. Study design aims to detect a 20% increase in overall survival after 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 tumor response rate, quality of life, KPS, steroid dose, and toxicity. Toxicity, objective tumor response rate, and QoL will be assessed every 3rd month. Endpoint data will be collected at the end of the trial, including the occurrence of suspected unexpected serious adverse reactions (SUSARs), unacceptable serious adverse events (SAEs), withdrawal of consent, or loss-to-follow-up. DISCUSSION: New treatment modalities are highly needed for first recurrence glioblastoma. Our proposed treatment modality of skull remodeling surgery, Tumor Treating Fields, and best practice medical oncological therapy may increase overall survival significantly. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0422399 , registered 13. January 2020.

Improved quality of Type 2 diabetes care following electronic feedback of treatment status to general practitioners: a cluster randomized controlled trial.

AIMS: To evaluate the effect of an electronic feedback system to general practitioners on quality of Type 2 diabetes care. METHODS: A cluster randomized, controlled trial with 15 months follow-up. Eighty-six general practices (158 general practitioners) in a Danish county caring for 2458 people 40-70 years old with Type 2 diabetes were randomized to receive or not to receive electronic feedback on quality of care. People with Type 2 diabetes were identified using a validated algorithm. Primary end-points were processes of care according to guidelines on prescriptions redeemed for Type 2 diabetes treatments, measuring of glycated haemoglobin and cholesterol and visits to ophthalmologists. Secondary end-points were changes in level of glycated haemoglobin and serum cholesterol. Data were analysed using generalized linear models accounting for clustering at practice level. RESULTS: During follow-up, people with Type 2 diabetes in the intervention group more often redeemed recommended prescriptions than people in the control group, respectively, as follows: oral antidiabetic treatment (32.8 vs. 12.0%, P =0.002), insulin treatment (33.8 vs. 12.4%, P < 0.001), lipid-lowering medication (38.3 vs. 18.6%, 0.004) and blood pressure medication (27.6 vs. 16.3%, P = 0.026). There were no differences in mean glycated haemoglobin and serum cholesterol between the two groups. CONCLUSIONS: Electronic feedback to general practitioners on the quality of Type 2 diabetes care resulted in significantly improved quality regarding processes of care according to guidelines. It was not possible to demonstrate any effect on secondary end-point measures within the follow-up period. Electronic feedback on quality of diabetes care can be effective in improving adherence to treatment according to evidence-based guidelines.