gms | German Medical Science

70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12.05. - 15.05.2019, Würzburg

Open-label phase 1 clinical trial testing personalised and targeted skull remodelling surgery to maximise TTFields intensity for recurrent glioblastoma – interim analysis and safety assessment (OptimalTTF-1)

Open-label Phase 1 Studie zur Untersuchung einer personalisierten und zielgerichteten Remodellierungsoperation zur Maximierung der TTFields Intensität beim rezidivierenden Glioblastom – Interim Analyse und Sicherheitsbewertung (OptimalTTF-1)

Meeting Abstract

  • Anders R. Korshoej - Aarhus University Hospital, Department of Neurosurgery, Arhus, Denmark; Odense University Hospital, Department of Neurosurgery, Odense, Denmark
  • S. Lukacova - Aarhus University Hospital, Department of Oncology, Aarhus, Denmark
  • J. H. Sørensen - Aarhus University Hospital, Department of Neurosurgery, Arhus, Denmark
  • F. L. Hansen - Aarhus University Hospital, Department of Neurosurgery, Arhus, Denmark
  • presenting/speaker Nicola Mikic - Aarhus University Hospital, Department of Neurosurgery, Arhus, Denmark
  • A. Thielcher - Danish Research Centre for Magnetic Resonance, Copenhagen, Denmark; Danish Technical University, Copenhagen, Denmark
  • S. O. S. Cortnum - Aarhus University Hospital, Department of Neurosurgery, Arhus, Denmark
  • T. L. Guldberg - Aarhus University Hospital, Department of Oncology, Aarhus, Denmark
  • Y. Lassen-Ramshad - Aarhus University Hospital, Department of Oncology, Aarhus, Denmark
  • C. Rahbek - Aarhus University Hospital, Department of Neuroradiology, Aarhus, Denmark
  • K. E. Severinsen - Aarhus University Hospital, Department of Neurology, Aarhus, Denmark
  • G. B. von Oettingen - Aarhus University Hospital, Department of Neurosurgery, Arhus, Denmark

Deutsche Gesellschaft für Neurochirurgie. 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie. Würzburg, 12.-15.05.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocV006

doi: 10.3205/19dgnc006, urn:nbn:de:0183-19dgnc0067

Veröffentlicht: 8. Mai 2019

© 2019 Korshoej et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objective: We present a pre-specified interim analysis of an ongoing open-label, investigator-sponsored phase 1 trial (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, burr-holes, and/or skull thinning personalized to enhance TTFields intensity focally in the tumor.

Methods: Eligibility: Age >18 years, first recurrence focal supratentorial GBM (RANO), and KPS ≥70. Personalized electric field calculations were conducted to validate TTFields enhancement > 25% by SR-surgery. Patients were right-censored for OS and PFS at the time of analysis and excluded upon progression, death, SUSARs, or unacceptable AEs. Primary endpoints: Toxicity (CTCAEv4.0). Secondary endpoints: OS, PFS, PFS6, objective response rate (iRANO), quality of life, KPS, and steroid dose.

Results: 16 patients were screened, 1 declined, and 2 had KPS<70. Of the 13 enrolled patients, 3 were excluded prior to TTFields treatment (1 female due to radionecrosis/non-recurrence, 1 male due to post-op infection, and 1 female due to neurological deficits). All included patients (9 male and 1 female) had GBM IDH-wt tumors (4 MGMT-methylated). Median age was 55 years (range 49 to 67). All patients received maximum safe resection at recurrence (4 had no residual tumor (RANO), 4 had non-measurable disease, and 2 had measurable disease). 8 patients received adjuvant bevacizumab monotherapy and 2 received temozolomide rechallenge. The mean skull-defect area was 10.5 cm2, the median field enhancement 37%. Within the observation period 5 patients had progression, 3 died, 5 were censored for PFS, and 7 for OS. We observed no SUSARs or grade 4/5 SAEs, but 5 grade 3 SAEs (2 generalized seizures in patients with known epilepsy, 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 OS was 15.5 months, 95%-CI: 5.9-NA, median PFS 9.5 months, 95%-CI: 3.7-NA, and PFS6 58%, 95%-CI: 0.27–0.90. 1 patient had complete response during TTFields treatment.

Conclusion: SR-surgery including craniectomy is not associated with additional toxicity in combination with TTFields and holds promising potential for improving TTFields outcome by focally enhancing the field intensity in the tumor. A future phase 2/3 trial is being planned for efficacy assessment.