Improving Tumor Treating Fields Treatment for Brain Cancer Patients With Skullremodeling Surgery (Neurosurgery)

The aim of this trial is to test a new potential treatment, skullremodeling surgery (SR-surgery) combined with tumor treating fields (TTFields), for patients with first recurrence of malignant brain tumor (first recurrence of glioblastoma). Glioblastoma is one of the most malignant cancers. TTFields is a new treatment for brain cancer (glioblastoma), which is used in additional to surgery (removal of the tumor), chemotherapy and radiation. TTFields work by sending alternating current to the tumor. The current disrupts cell division and thus prevents cancer growths. Electrodes are placed on the scalp and the current is delivered via a small portable battery (1kg). Treatment duration is 18 hours during the day, where the patient can do normal daily activities. The average life expectancy of a newly diagnosed brain cancer patient (glioblastoma) is increased from 15 months to 21 months by adding TTFields. SR-surgery is a minor and safe procedure, that involves creating small burrholes in the skull over the tumor location. The burrholes are approximately 15 mm in diameter. The burrholes increase the electric current in the tumor by funneling the electricity trough the path of least resistance, since bone hinders the electricity. The theory is that combining TTFields with SR-surgery we can increase the effect of TTFields and in return increase overall survival for brain cancer patients. The investigators have recently finished a phase 1 clinical trial, with 15 trial participants, testing the safety and efficacy of our combined treatment. The investigators concluded that TTFields and SR-surgery combined is safe and showed promising results by increasing overall survival with the trial participants. Therefor we wish to proceed with a phase 2 trial. Method The investigators aim to include 70 patients with first recurrence of glioblastoma (brain cancer). Each patient will be randomized to one of two treatment arms. Both treatment arms will receive the best current brain tumor treatment. In addition, one arm receives TTF and the other arm TTFields and SR-surgery. All patients are expected to receive better treatment than current best practice, since TTFields is not standard treatment in Denmark. The primary aim of the trial is to assess the 12-month overall survival in both groups. The theory is that more trial participants will be alive after 12 months in the group that receives both TTF and SR-surgery. The trial duration is 36 months with an average expected follow-up of 18 months.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. age 18 years or older
2. progressive GBM based on the RANO criteria and whole brain MRI according to the consensus recommendations for a standardized brain tumor imaging protocol in clinical trials , not older than 4 weeks from the assessment
3. estimated survival≥ 3 months
4. supratentorial tumor location
5. focal disease in the vicinity of the previously known tumor or resection cavity,
6. KPS≥70
7. ability to comply with TTFields treatment
8. eligibility for diagnostic or therapeutic neurosurgery and subsequent best practice oncological therapy,
9. tumor characteristics indicating significant expected benefit from feasible craniectomy or SR-surgery combined with TTFields i.e. (a) focal tumor and (b) most superficial border of tumor or resection cavity closer than 2 cm from brain surface
10. use of validated anticonception for fertile female participants in concordance with guidelines provided by the danish health and medicines authority,
11. signed written consent form

Exclusion Criteria:

1. pregnancy or nursing (fertile female participants will be required to take a validated pregnancy test for evaluation of pregnancy)
2. infra-tentorial tumor
3. implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmia
4. uncontrollable symptomatic epilepsy refractory to standard medication
5. contraindications for skullremodeling surgery, e.g.bleeding diathesis or severe infection
6. significant co-morbidities, i.e. (a)significant liver function impairment (alt \>210 u/l for men and \> 135 u/l for women or total bilirubin \>25umol/l), (b)significant renal impairment (serum creatinine \> 1.7 mg/dl= 150 umol/l), (c)coagulopathy (inr\> 1.8 or aptt \> 57s), (d) thrombocytopenia (platelet count \< 100 x 103/μl =100 x 109/l), (e) neutropenia (anc\< 1.5 x 103/μl =1.5 x 109/l), (f) anemia ( hb \< 10 g/l= 6.0 mmol/l)
7. severe cognitive impairment
8. active participation in another therapeutic interventional clinical trial