Evaluation of the safety and effectiveness of using Exablate to open the Blood Brain Barrier for the carboplatin passage to the tumour for the treatment of recurrent glioblastoma (rGBM)

Phase 1

• Conditions: Recurrent Glioblastoma (rGBM); MedDRA version: 20.0Level: PTClassification code 10018337Term: Glioblastoma multiformeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-003127-41-IT
• Lead Sponsor: INSIGHTEC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-07
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1.Have histologically confirmed recurrent glioblastoma or clear MRI images of rGBM (T2/FLAIR abnormality consistent with tumor-associated edema that may also demonstrate additional features consistent with infiltrating high grade glioma e.g.: restricted diffusion; increase blood flow or volume on perfusion imaging)
2.Be =18 years and < 80 years of age on day of signing informed consent.
3.Karnofsky Performance Status (KPS) = 70
4.Recurrence after first line therapy with temozolomide and radiotherapy
5.CT within 30 days of first Exablate procedure and MRI within 14 days prior to first Exablate procedure.
6.An interval of at least 3 weeks (prior to first Exablate BBBD) between prior surgical resection at recurrence or one week for stereotactic biopsy.
7.An interval of at least 12 weeks from the completion of radiation therapy to first Exablate procedure unless there is unequivocal histologic confirmation of tumor progression or radiographic progression outside of the prior radiation field.
8.Must have recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy (exceptions include but not limited to alopecia, laboratory values not listed per inclusion criteria, and lymphopenia which is common after therapy with temozolomide).
9.Prior to first Exablate procedure, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies. No wash-out period required for prior TTF or vaccine therapies.
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.Prior unacceptable toxicity with carboplatin therapy.
2.Subjects with cerebellar or brainstem tumor.
3.Subjects with diagnosis of immunodeficiency, known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected), or known positive HIV status.
4.Significant depression not adequately controlled with medication and at potential risk of suicide. Subjects on antipsychotic, antidepressants and benzodiazepines may be allowed to continue. Exposure of these medication will be limited for up to 48 hrs prior to ExAblate BBBD when medically feasible; patient will be monitored closely as indicated.
5.Has received anti-VEGF or anti-VEGFR targeted agents (e.g. bevacizumab, cedirinab, aflibercept, vandetanib, XL-184, sunitinib, etc).
6.Prior locally delivered therapies including chemotherapy wafers, immunotoxins delivered by convection-enhanced delivery, regionally administered gene and viral therapies, focal irradiation with brachytherapy, stereotactic radiosurgery, laser interstitial thermotherapy
7.Cardiac disease or unstable hemodynamics
8.Anti-coagulant therapy, or medications known to increase risk of hemorrhage within washout period prior to treatment
9.History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage.
10.Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis.
11.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.
12.Severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 and/or on dialysis.
13.Subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation, or QT prolongation observed on screening ECG (QTc > 450 for men and >470 for women).
14.Has a known additional malignancy that is progressing or requires active treatment within 2 years of consent. Exceptions include malignancies treated with surgery alone including but not limited to basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
15.Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Examples include, but are not limited to, active infection requiring systemic therapy or psychiatric illness/social situations that would limit compliance with study requirements

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: The purpose of this study is to evaluate the safety and feasibility of the Exablate Model 4000 Type 2.0/2.1 when used as a tool to disrupt the blood brain barrier (BBB) in subjects with recurrent glioblastoma (rGBM) undergoing carboplatin monotherapy;Secondary Objective: Not applicable;Primary end point(s): Safety<br>Safety of the BBBD procedure will be evaluated through patient examination and magnetic resonance image (MRI) assessments during the treatment and during clinical visits. Serial clinic visits including physical and neurologic examination as well as periodic MRI scans will be used to continuously monitor safety post-BBBD procedures after adjuvant carboplatin monotherapy + Exablate BBBD is completed.;Timepoint(s) of evaluation of this end point: Refer to clinical protocol for timepoints