Feasibility study of BBB opening
- Conditions
- Recurrent Glioblastoma (rGBM)rGBMD005909
- Registration Number
- JPRN-jRCTs052220021
- Lead Sponsor
- Kishima Haruhiko
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 5
1. Have histologically confirmed recurrent glioblas toma or clear MRI images of rGBM and prior expla nation of prognosis (T2/FLAIR abnormality consist ent with tumor-associated edema that may also de monstrate additional features consistent with infilt rating high grade glioma e.g.: restricted diffusion; i ncrease blood flow or volume on perfusion imagin g).
2. Subjects with planned Carboplatin therapy.
3. Be willing and able to provide written informed consent/assent for the trial.
4. Be 18 years and < 80 years of age on day of sig ning informed consent.
5. Karnofsky Performance Status (KPS) 70.
6. Recurrence after first line therapy with temozolomide and radiotherapy.
7. Screening labs (performed within 14 days of the first procedure) demonstrate adequate organ func
tion as defined
8. CT within 30 days of first Exablate procedure an d MRI within 14 days prior to first Exablate proced ure.
9. An interval of at least 3 weeks (prior to first Exa blate BBBD) between prior surgical resection at re currence or one week for stereotactic biopsy.
10. An interval of at least 12 weeks from the compl etion of radiation therapy to first Exablate procedu re unless there is unequivocal histologic confirmat ion of tumor progression or radiographic progressi on outside of the prior radiation field.
11. Participants must have recovered to grade 0 o r 1 or pre-treatment baseline from clinically signifi cant toxic effects of prior therapy (exceptions inclu de but not limited to alopecia, laboratory values n ot listed per inclusion criteria, and lymphopenia w hich is common after therapy with temozolomide).
12. Prior to first Exablate procedure, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic t herapy (except 23 days for temozolomide and 6 w eeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) fr om other anti-tumor therapies. No wash-out perio d required for prior TTF or vaccine therapies.
13. Female subject is confirmed NOT PREGNANT each procedure day. Male and Female subjects ar e utilizing highly effective contraception during th e study and through 120 days (4 months) after the study.
14. Able to communicate verbally (in order to ens ure adequate monitoring during the Exablate BBB D procedure)
1. Subjects presenting with the following imaging characteristics
a. Evidence of acute intracranial hemorrhage.
b. Containing calcifications in the focused ultraso und sonication beam path in the event system tool cannot tailor the treatment around these calcificat ion spots.
c. Evidence of midline shift evidence of subfalcine
, uncal, or tonsillar herniation on pre operative imaging or evidence of increased intracranial pres sure, such as herniation.
2. The sonication pathway to the tumor involves more than 30 percent of the skull area traversed by t
he sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp.
3. Ferrous metallic implanted objects in the skull o r the brain.
4. Prior unacceptable toxicity with carboplatin the rapy.
5. Subject is pregnant or breastfeeding.
6. Subjects with cerebellar or brainstem tumor.
7. Subjects with diagnosis of immunodeficiency, k nown active Hepatitis B (e.g., HBsAg reactive) or H epatitis C (e.g., HCV RNA (28) is detected), or kno wn positive HIV status.
8. Significant depression not adequately controlle d with medication and at potential risk of suicide. Subjects on antipsychotic, antidepressants and be nzodiazepines may be allowed to 27 Version Date October 13, 2020 Insightec Confidential continue. Exposure of these medication will be limited for u p to 48 hrs prior to ExAblate BBBD when medically feasible patient will be monitored closel y as indicated.
9. Has received anti VEGF or antiVEGFR targeted a gents (e.g. bevacizumab, cedirinab, aflibercept, va ndetanib, XL184, sunitinib, etc).
10. Subjects receiving treatment with corticosteroi d doses greater than dexamethasone 4 mg daily (o r equivalent).
11. Prior locally delivered therapies including che motherapy wafers, immunotoxins delivered by con vection enhanced delivery, regionally administered gene and viral therapies, focal irradiation with brachytherapy, stereotactic radios urgery, laser interstitial thermotherapy.
12. Cardiac disease or unstable hemodynamics i ncluding
a. Documented myocardial infarction within si x months of enrollment.
b. Unstable angina on medication.
c. Congestive heart failure.
d. Left ventricular ejection fraction less than 50 pe rcent.
e. History of a hemodynamically unstable cardiac arrhythmia.
f. Cardiac pacemaker.
g. Severe hypertension (diastolic BP more than 10 0 despite standard anti-hypertensive therapy).
13. Anti coagulant therapy, or medications known to increase risk of hemorrhage within washout peri od 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).
14. History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhag e.
15. Cerebral or systemic vasculopathy, including i ntracranial thrombosis, vascular malformation, cer ebral aneurysm or vasculitis.
16. Evidence of new focal neurological deficits incl uding, but not limited to, motor weakness or spee ch impairment within 7 to14 days prior to the first BBBD procedure.
17. Active drug or alcohol use disorder.
18. Refractory epilepsy (uncontrolled seizures des pite medical treatment) for a minimum of 4 weeks prior to first cycle or Exablate BBBD procedure ca ptured by history.
19. Known sensitivity to gadolinium.
20. Known sensitivity to microbubble resonators ( DEFINITY) ultrasound contrast agent or perflutren.
21. Unable to unde
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety of the BBB open procedure will be evaluate d through patient examination and MRI assessmen ts during the treatment and during clinical visits. Feasibility of BBB open will be evaluated through assessment of post-sonication contrast- enhanced MR imaging and comparing it with pre-sonication i maging.
- Secondary Outcome Measures
Name Time Method The preliminary effectiveness using modified RANO criteria and, Progression-Free Survival (PFS) and Overall Survival (OS)