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.

Autor: Mikic N; Department of Neurosurgery, Aarhus University Hospital, Palle Juul-Jensens Blvd 165, 8200, Aarhus, Denmark. nikmik@rm.dk.; Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Blvd. 82, 8200, Aarhus, Denmark. nikmik@rm.dk., Poulsen FR; Department of Neurosurgery, Odense University Hospital, Kløvervænget 47, 5000, Odense, Denmark.; Clinical Institute BRIDGE (Brain Research InterDisciplinary Guided Excellence), University of Southern Denmark, Winsløwparken 19, 5000, Odense, Denmark., Kristoffersen KB; Department of Oncology, Aarhus University Hospital, Palle Juul-Jensens Blvd. 99, 8200, Aarhus, Denmark., Laursen RJ; Department of Neurosurgery, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark., Guldberg TL; Department of Oncology, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark., Skjøth-Rasmussen J; Department of Neurosurgery, Rigshospitalet, Inge Lehmanns Vej 6, 2100, København Ø, Denmark., Wong ET; Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA.; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA., Møller S; Department of Oncology, Rigshospitalet, Blegdamsvej 9, 2100, København Ø, Denmark., Dahlrot RH; Department of Oncology, Odense University Hospital, Kløvervænget 19, 5000, Odense, Denmark., Sørensen JCH; Department of Neurosurgery, Aarhus University Hospital, Palle Juul-Jensens Blvd 165, 8200, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Blvd. 82, 8200, Aarhus, Denmark., Korshøj AR; Department of Neurosurgery, Aarhus University Hospital, Palle Juul-Jensens Blvd 165, 8200, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Blvd. 82, 8200, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2021 Sep 09; Vol. 21 (1), pp. 1010. Date of Electronic Publication: 2021 Sep 09.
DOI: 10.1186/s12885-021-08709-4
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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