NIPH Clinical Trials Search

JAPANESE
国立保健医療科学院
JRCT ID: jRCTs052220021

Registered date:02/05/2022

Feasibility study of BBB opening

Basic Information

Recruitment status Recruiting
Health condition(s) or Problem(s) studiedRecurrent Glioblastoma (rGBM)
Date of first enrollment02/05/2022
Target sample size5
Countries of recruitmentUSA,Japan,Canada,Japan,Italy,Japan,Spain,Japan,Israel,Japan,South Korea,Japan
Study typeInterventional
Intervention(s)Administration of Carboplatin and treatment by Ex Ablate 4000 type 2 for BBB open

Outcome(s)

Primary OutcomeSafety 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 OutcomeThe preliminary effectiveness using modified RANO criteria and, Progression-Free Survival (PFS) and Overall Survival (OS)

Key inclusion & exclusion criteria

Age minimum>= 18age old
Age maximum< 80age old
GenderBoth
Include criteria1. 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)
Exclude criteria1. 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 undergo MRI or contraindications to MRI such as non MRI compatible implanted device s. 22. Difficulty lying supine and still for up to 4 hour s in the MRI unit or severe claustrophobia which c annot be managed with medication. 23. Severely impaired renal function with estimate d glomerular filtration rate less than 30 mLmin1.73 m2 and or on dialysis. 24. Right to left or bidirectional cardiac shunt. 25. Subjects with evidence of cranial or systemic i nfection requiring antibiotics. 26. Subjects with a family or personal history of Q T prolongation or taking concomitant medications known to cause QTc prolongation, or QT prolonga tion observed on screening ECG (QTc more than 4 50 for men and more than 470 for women). 27. Has a known additional malignancy that is pro gressing or requires active treatment within 2 year s of consent. Exceptions include malignancies trea ted with surgery alone including but not limited to basal cell carcinoma of the skin, squamous cell car cinoma of the skin, or in situ cervical cancer that h as undergone potentially curative therapy. 28. Has a history or current evidence of any condit ion, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subjects participation for the full duration of the tri al, or is not in the best interest of the subject to pa rticipate, in the opinion of the treating investigator. Examples include, but are not limited to, active inf ection requiring systemic therapy or psychiatric ill ness or social situations that would limit compliance with study requirements.

Related Information

Contact

Public contact
Name Noriyuki Kijima
Address 2-15 Yamadaoka, Suita, Osaka, Japan Osaka Japan 565-0871
Telephone +81-6-6879-3650
E-mail kijima0913@nsurg.med.osaka-u.ac.jp
Affiliation Osaka University Hospital
Scientific contact
Name Haruhiko Kishima
Address 2-15 Yamadaoka, Suita, Osaka, Japan Osaka Japan 565-0871
Telephone +81-6-6879-3650
E-mail hkishima@nsurg.med.osaka-u.ac.jp
Affiliation Osaka University Hospital