Enhancing Optune Therapy With Targeted Craniectomy

Study Overview
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Brief Summary
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The present study proposes a new and potentially superior clinical approach to Optune™ therapy of selected glioblastoma patients. The approach is based on combining TTFields with targeted surgical skull remodeling, such as minor craniectomy or a distribution of burr holes, designed for the individual patient. Pre-clinical modeling results suggest that such procedures may enhance the induced electrical field strength by up to  100% and thereby potentially improve the clinical outcome of treated patients to a significant extent. The study is an open label phase 1 clinical pilot experiment designed to investigate feasibility, safety and efficacy of the concept. Fifteen patients with first recurrence of glioblastoma will be included in the trial. All patients will receive TTFields therapy with targeted craniotomy and best physician's choice chemotherapy.

Official Title
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Enhancing Optune Therapy of Recurrent Glioblastoma Multiforme Using Targeted Surgical Skull Remodeling

Conditions
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Glioblastoma

Intervention / Treatment
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* Device: Optune
* Procedure: Craniectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological evidence of GBM using WHO classification criteria Estimated survival minimum three months Supratentorial tumor Not a candidate for further radiotherapy First disease recurrence in accordance with RANO criteria Karnofsky scale score minimum 70 Ability to comply with Optune therapy Tumor characteristics which indicate significant expected benefit from feasible craniotomy or skull remodelling surgery combined with TTFields Focal tumor Most superficial border of tumor or resection cavity closer than 2 cm from brain surface Use of validated anti-conception for female participants in accordance with guidelines provided by the Danish Health and Medicines Authority Signed written consent form Exclusion Criteria: Pregnancy or nursing. Fertile female participants will be required to take a validated pregnancy test for evaluation of pregnancy Less than four weeks since radiation therapy Infratentorial tumor Implanted pacemaker, programmable shunt, defibrillator, deep brain stimulator, other implanted devices in the brain, or documented clinically significant arrhythmias. Uncontrollable symptomatic epilepsy, refractory to standard medication. Epilepsy will not necessarily contraindicate participation in the trial as this is a common complication to the disease. Eligibility will be determined by the examining physician and investigators in conjunction upon careful consideration of patient safety. Contraindications for skull remodelling surgery, e.g. bleeding diathesis or severe infection. Significant co-morbidities (within four weeks prior to enrolment) Significant liver function impairment - ALT > 3 times the upper limit of normal Total bilirubin > upper limit of normal Significant renal impairment (serum creatinine > 1.7 mg/dL) Coagulopathy (as evidenced by PT or APTT > 1.5 times control in normal individuals not undergoing anticoagulation) Thrombocytopenia (platelet count < 100x10^3/μL ) Anemia (Hb < 10 g/L) Active participation in another clinical treatment trial Patients will be regarded as participants when they have signed a consent form and have been found suitable for enrolment by the examining physician, in accordance with the abovecriteria. Patients may receive medication depending on their clinical condition and other diseases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Craniectomy and Optune<br>Patients will receive best physician's choice chemotherapy along with Optune therapy and craniotomy surgery. Optune therapy will be administered in the standard configuration and in accordance with current guidelines with the exception of the surgical intervention. | Device: Optune<br>* For further information see www.optune.com<br>* Other names: TTFields;Procedure: Craniectomy<br>* A small hole is placed in the skull between the tumor and the closest Optune electrode. The position and geometry of the craniotomy is determined by computersimulation of the electric field induced by Optune therapy. Craniotomy is a surgical procedure, which is carried out under general anaesthesia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of serious adverse events | Based on CTCAE. | Through study completion, an average of 18 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Through study completion, an average of 18 months. | 
| Progression free survival |  | Through study completion, an average of 18 months. | 
| Progression free survival at six months |  | Through study completion, an average of 18 months. | 
| % 1-year survival |  | Through study completion, an average of 18 months. | 
| Objective response rate | Assessed by RANO criteria | Will be assessed at baseline and upon clinical follow-up every 3rd month until exclusion. Data will be presented at trial termination. | 
| Quality of life | Assessed by EORTC QLQ-30 and QLQ-BN20 | Will be assessed at baseline and upon clinical follow-up every 3rd month until exclusion. Data will be presented at trial termination. | 
| Cumulative corticosteroid dosage |  | Will be assessed at baseline and upon clinical follow-up every 3rd month until exclusion. Data will be presented at trial termination. | 
| Karnofsky performance score |  | Will be assessed at baseline and upon clinical follow-up every 3rd month until exclusion. Data will be presented at trial termination. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tumour treating fields, Optune, Craniectomy, TTFields