Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Real-world data on melanoma brain metastases and survival outcome

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Implementation of TERT promoter mutations improve prognostication of the WHO classification in meningioma

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Patients with cirrhosis have elevated bone turnover but normal hepatic production of osteoprotegerin

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Dipeptidyl peptidase-3 is associated with severity of liver disease and circulatory complications in patients with cirrhosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. A new uPAR-targeting fluorescent probe for optical guided intracranial surgery in resection of a meningioma-a case report

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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.

Original languageEnglish
Article number1010
JournalBMC Cancer
Volume21
Issue number1
Pages (from-to)1010
ISSN1471-2407
DOIs
Publication statusPublished - 9 Sep 2021

Bibliographical note

© 2021. The Author(s).

    Research areas

  • Adult, Brain Neoplasms/surgery, Follow-Up Studies, Glioblastoma/mortality, Humans, Karnofsky Performance Status, Neoplasm Recurrence, Local/mortality, Osteotomy/methods, Progression-Free Survival, Prospective Studies, Quality of Life, Skull/surgery, Time Factors, Transducers

ID: 68904018