Background: We present a clinical open label, phase-1 trial (OptimalTTF-1, NCT02893137), which aims to test a novel treatment for first recurrence glioblastoma (rGBM). The aim of the treatment is to optimize the electric field generated by Tumor Treating Fields (TTFields) with targeted and individualized skull-remodeling surgery (SR-surgery). Selectively placed burrholes reduces the electric resistance created by the bone and thus improves the electric field focally. Preclinical research has indicated this conclusion. The final analysis examined the toxicity and efficacy of this combined intervention in addition to best practice chemotherapy.
Methods: Trial period was from Dec2016 to Mar2019. Primary endpoint was the frequency of adverse events (CTCAEv4.0) and secondary endpoints were overall survival and progression-free survival.Major eligibility: ≥18-years, focal supratentorial rGBM, KPS≥70, and a minimum calculated increase in TTFields strength of ≥25% after SR-surgery. At the time-of-analysis patients were censored for time-to-event endpoints.
Results: 15 patients (11M/4F) were included out of the 18 screened. Patient baseline (median, (range)) showed, age 57(39;67), skull defect area=10.6cm2(7;37) and improved TTFields strength by 43%(25;59). All tumors were IDH-wt and 4 had MGMT methylation. Four were excluded before initiation of TTFields (withdrawal of consent, radionecrosis, postoperative infection and cognitive deficit). Therefor 11 underwent the treatment. TTFields compliance was 90% (48;98), treatment duration 6.8months(2.3;20.4) and average follow-up was 10months.Regarding toxicity, grade 3 AE was the highest recorded with 12 episodes (6 seizures, 1 headache, 1 fatigue, 1 TIA, 1 diarrhea, 1 DVT and 1 postop infection. Most common AE grade 1-2 was headache 60% CI95%=[32;84], fatigue 53%, CI95%=[27;79], skin rash 47%, CI95%=[21;73], and nausea 40%, CI95%=[16;68]. Regarding survival following was observed, OS=15.0 months, CI95%=[9.6;16.2], and OS12=64%, CI95%=[35;85], PFS=8.8 months, CI95%=[6.2;13.2] and PFS6=64%, CI95%=[35;85].
Conclusion: TTFields coupled with SR-surgery is safe and does not give additional toxicity. Trial data indicates improved overall survival in rGBM. More research is needed, which is why a phase 2 clinical trial is underway (NCT04223999).
Citation Format: Nikola Mikic, Anders R. Korshøj, Slavka Lukacova, Jens C. Sørensen, Frederik L. Hansen, Axel Thielscher, Søren O. Cortnum, Trine L. Guldberg, Yasmin Ramshad-Lassen, Christian Rahbek, Kåre Eg Severinsen, Gorm von Oettingen. Final results for OptimalTTF-1: Optimizing Tumor Treating Fields with targeted skull remodeling surgery for first recurrence glioblastoma: Phase 1 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 CT103.