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Enhancing Optune Therapy With Targeted Craniectomy

Phase 1
Completed
Conditions
Glioblastoma
Interventions
Device: Optune
Procedure: Craniectomy
Registration Number
NCT02893137
Lead Sponsor
Aarhus University Hospital
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
15
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Craniectomy and OptuneOptunePatients 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.
Craniectomy and OptuneCraniectomyPatients 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.
Primary Outcome Measures
NameTimeMethod
Frequency of serious adverse eventsThrough study completion, an average of 18 months.

Based on CTCAE.

Secondary Outcome Measures
NameTimeMethod
% 1-year survivalThrough study completion, an average of 18 months.
Cumulative corticosteroid dosageWill be assessed at baseline and upon clinical follow-up every 3rd month until exclusion. Data will be presented at trial termination.
Overall survivalThrough study completion, an average of 18 months.
Progression free survivalThrough study completion, an average of 18 months.
Progression free survival at six monthsThrough study completion, an average of 18 months.
Objective response rateWill be assessed at baseline and upon clinical follow-up every 3rd month until exclusion. Data will be presented at trial termination.

Assessed by RANO criteria

Quality of lifeWill be assessed at baseline and upon clinical follow-up every 3rd month until exclusion. Data will be presented at trial termination.

Assessed by EORTC QLQ-30 and QLQ-BN20

Karnofsky performance scoreWill be assessed at baseline and upon clinical follow-up every 3rd month until exclusion. Data will be presented at trial termination.

Trial Locations

Locations (1)

Aarhus University Hospital

🇩🇰

Aarhus C, Aarhus, Denmark

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