ACTR-43. OPEN-LABEL PHASE 1 CLINICAL TRIAL TESTING PERSONALIZED AND TARGETED SKULL REMODELING SURGERY TO MAXIMIZE TTFIELDS INTENSITY FOR RECURRENT GLIOBLASTOMA – INTERIM ANALYSIS AND SAFETY ASSESSMENT (OPTIMALTTF-1) Article Swipe

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Medicine Temozolomide Interim analysis Bevacizumab Adverse effect Internal medicine Surgery Oncology Progression-free survival Clinical trial Chemotherapy

Anders Rosendal Korshoej , Slávka Lukacova , Jens Christian Hedemann Sørensen , Frederik Lundgaard Hansen , Nikola Mikic , Axel Thielscher , Søren Cortnum , Trine Lignell Guldberg , Yasmin Ramshad-Lassen , Christian Rahbek , Kåre Eg Severinsen , Gorm von Öettingen ·

YOU? · · 2018 · Open Access · · DOI: https://doi.org/10.1093/neuonc/noy148.075 · OA: W2889561152

We present a pre-specified interim analysis of an ongoing open-label, phase-1 IST (NCT02893137) testing safety/efficacy of a new rGBM treatment. The intervention combines personalized skull-remodeling (SR) surgery with TTFields and best-choice chemotherapy. SR-surgery involves minor craniectomy or burr-holes personalized to enhance TTFields intensity focally in the tumor. Accrual began Dec 2016 (planned total 15 patients). Eligibility: Age > 18 years, first recurrence focal supratentorial GBM (RANO), and KPS 70. Patients were excluded upon progression, death, SUSARs, or unacceptable AEs. Primary endpoints: Toxicity (CTCAEv4.0). Secondary endpoints: OS, PFS, PFS6, ORR (iRANO). Interim analysis was based on data prior to April 1, 2018. 16 patients were screened, 1 declined, and 2 had KPS < 70. 3 patients were excluded prior to TTFields (radionecrosis/non-recurrence, post-op infection, and neurodeficit, respectively). All included patients (10, M/F 9:1) had GBM IDH-wt tumors (4 MGMT-methylated). Median baseline variables were KPS 90 (range 70–100), age 55 years (range 49 to 67), skull-defect area 10.5 cm2 (range 7 to 24), field enhancement 37 % (range 25 to 61), and TTFields compliance 91% (range 61 to 95). All patients received maximum safe resection (4 had non-measurable and 2 measurable disease). 8 patients received adjuvant bevacizumab and 2 temozolomide rechallenge. 5 patients had progression, 3 died, 5 were censored for PFS and 7 for OS. We observed no SUSARs, no grade 4/5 SAEs, 5 grade 3 SAEs (2 generalized seizures, 1 post-op infection, 1 diarrhea, and 1 DVT). 2 patients had grade 1–2 skin rash, and 1 had grade 1–2 headaches. Median outcome estimates: OS 15.5 months, 95%-CI: 5.9-NA, PFS 9.5 months, 95%-CI: 3.7-NA, and PFS6 58%, 95%-CI: 0.27–0.90. 1 patient had complete response. SR-surgery with TTFields is non-toxic and holds promising potential for improving rGBM outcome. A future phase 2/3 trial is being planned.