Evaluation of the safety and effectiveness of using Exablate to open the Blood Brain Barrier to allow standard chemotherapy passage to the tumour for the treatment of high grade glioma

Phase 1

• Conditions: Glioblastoma; MedDRA version: 20.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004851-34-IT
• Lead Sponsor: INSIGHTEC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-04
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Patient is eligible for adjuvant TMZ treatment based on the current standard of care.
2. Men or women age between 18 and 80 years, inclusive.
3. Able and willing to give informed consent.
4. Grade IV glioma (GBM) confirmed through assessment of surgical specimens by a board-certified neuropathologist.
5. Maximal surgical debulking of the tumor was performed.
6. Combined radiation/TMZ treatment is completed based on the prescribed standard of care regimen.
7. Karnofsky rating 70-100 (See Appendix B).
8. Able to communicate during the Exablate BBBD procedure.
9. Life expectancy of at least 3 months.
10. Contraceptive use by both male and female subjects consistent with local regulations regarding the methods of contraception for those participating in clinical studies (See section 2.5 point 10).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1. Patients presenting with the following imaging characteristics:
i.Evidence of acute intracranial hemorrhage.
2.The sonication pathway to the tumor involves:
i.More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp.
3.The subject presents with severe symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papilledema).
4.Sever midline shift or evidence of subfalcine, uncal, or tonsillar herniation on pre-procedure imaging.
5.Patients with cerebellar or brainstem tumors.
7.Significant depression not adequately controlled with medication and at potential risk of suicide.
8.Patients with brain tumors containing 1p/19q chromosomal co-deletion (consistent with oligodendroglioma).
9.Patient receiving bevacizumab (Avastin) therapy.
10.Patients receiving treatment with corticosteroid doses greater than dexamethasone 24mg daily (or equivalent).
11.Patients undergoing other concurrent therapies such as chemotherapy wafers, immunotoxins delivered by convection-enhanced delivery, regionally administered gene and viral therapies, immunotherapies, focal irradiation with brachytherapy, stereotactic radiosurgery, laser interstitial thermotherapy, and tumor treatment fields therapy. These regimens have been shown to cause contrast enhancement in the resection cavity boundary, which can be difficult to differentiate from true tumor recurrence [35] [36], [37-39].
12.Anti-coagulant therapy, or medications known to increase risk of hemorrhage within washout period prior to treatment (i.e., antiplatelet or vitamin K inhibitor anticoagulants within 7 days, non-vitamin K inhibitor anticoagulants within 72 hours, or heparin-derived compounds within 48 hours of treatment).
13.History of a bleeding disorder and/or coagulopathy.
14.Abnormal level of platelets (< 100,000) or INR > 1.3.
15.Cerebral vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis.
16.Evidence of new focal neurological deficits including, but not limited to, motor weakness or speech impairment within 7-14 days prior to the first BBBD procedure.
17.Severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 and/or on dialysis.
18.Right to left or bi-directional cardiac shunt.
19.Subjects with evidence of cranial or systemic infection.
20.Subjects with significant liver dysfunction, e.g., history of cirrhosis (hemochromatosis or severe alcohol abuse), or active hepatitis (autoimmune or infectious) with elevated AST, ALT INR or bilirubin (ALT: Male 21-72 units/L; Female 9-52 units/L; AST: Male 17-59 units/L, Female 14-36 units/L; INR >1.3; bilirubin >5 times lab normal).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified