recurrent glioblastoma multiforme recurrent braintumor
Conditions
Interventions
This study utilizes Yttrium-90 (Y90) glass microspheres, an investigational radiotherapeutic device composed of microscopic, insoluble glass beads embedded with the radioactive isotope Y90. These micr
Sponsors
Boston Scientific International SA
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: All of the following inclusion criteria must be met: Subject is 18 years or older and has signed and dated the trial informed consent form (ICF) Life expectancy = 12 weeks Subject is willing and able to comply with the trial testing, procedures, and follow-up schedule History of a histologically confirmed diagnosis of glioblastoma per 2021 WHO criteria Have radiographic evidence of measurable tumor progression/recurrence according to RANO 2.0 criteria Target lesion volume does not exceed 70 cm3 Prior surgery and treatment with combination of radiotherapy and chemotherapy + Tumor Treating Fields (Optune®) ECOG performance status = 2 The interval since completion of external beam cranial radiotherapy must be > 6 months, unless there is confirmation of tumor recurrence/progression outside the previous radiation treatment field, in which case the interval since completion of cranial radiation must be at least 12 weeks Interval since last systemic therapy until index procedure = 4 weeks since last dose of temozolomide = 4 weeks since last dose of lomustine or other nitrosourea = 2 weeks since last dose of any oral targeted therapy (Tyrosine Kinase inhibitor or similar) = 6 weeks from last dose of last intravenous bevacizumab infusion, or other antibody-based anti VEGF therapy = 4 weeks since last dose of investigational agents or patient has on-going < Grade 2 AEs related to investigational agent. If receiving steroids, patient should be on a stable or decreasing dose equivalent to dexamethasone = 6 mg/d, for at least 7 days prior to index procedure Have adequate organ and bone marrow function within 14 days prior to index procedure, as defined below: INR = 1.5 (in absence of anticoagulation) Platelets = 75,000/L Creatinine =1.5 mg/dL Absolute Neutrophil Count =1.5 x 109/L Hemoglobin =9.0 g/dL For female of child-bearing potential: Have a negative pregnancy test within 14 days prior to index procedure If sexually active must be using, or agree to use, an acceptable method of birth control as confirmed by the investigator If currently breastfeeding, must agree to stop breastfeeding Angiographic Inclusion Criteria: The intent of therapy should be to encompass the entire radiographically defined target lesion within the PV Each PV is = 150cc, with the total PV not exceeding 400cc
Exclusion criteria
Exclusion criteria: None of the following exclusion criteria can be met: Have leptomeningeal disease or other primary malignancy metastatic to the brain Target lesion located in or involving the infratentorial space, thalamus, hypothalamus, internal capsule, or optic chiasma Have received more than 1 course of prior cerebral radiotherapy (EBRT) Prior cranial radiation dose = 66 Gy Have received radiosurgery, brachytherapy, or hypofractionated radiotherapy Have received more than 2 systemic anti-tumor treatment protocols (lines of treatment), not including neoadjuvant or adjuvant temozolomide (oral or IV) Have received more than 2 surgical GBM-related procedures Patients with a history of stroke, ischemic cerebral disease, and/or at risk of cerebral herniation Are at increased risk of wound dehiscence by the discretion of the investigators (e.g. recent brain surgery, poor skin condition, and/or previously infected surgical field or any other condition that is of increased infectious risk in the opinion of the treatment team) Have uncontrolled epilepsy Have severe and/or insufficiently controlled intercurrent illness; patients with the following are not eligible: Hypertension grade 3 or higher without adequate control on medications Symptomatic or unstable cardiac disease Ongoing or active bacterial or viral infection requiring systemic treatment (including HIV) Psychiatric illness/social situations that would limit compliance with study requirements Peripheral Neuropathy = grade 1 Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient’s safety or study endpoints Patients with a history of an active other malignancy within 1 year prior to index procedure. NOTE: Exceptions to this requirement include adequately treated non-melanoma skin cancer or carcinoma in situ without evidence of disease Medical contraindication to undergo contrast-enhanced magnetic resonance imaging (MRI) Known history of severe uncorrectable reactions to iodinated and/or gadolinium-based contrast Subject is currently participating, or plans to participate in, another investigational trial that may confound the results of this trial (unless written approval is received from the Boston Scientific study team) Angiographic Exclusion Criteria: Patients with evident AV shunting, vascular disease or tortuosity precluding safe or feasible vascular access, or patient vasculature not conducive to delivery of the therapy on baseline imaging or angiography.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Maximum Tolerated Radiation Absorbed Dose (MTRAD) of Yttrium-90 (Y-90) microspheres to the perfused volume (PV) is defined as the dose associated with a Dose-Limiting Toxicity (DLT) rate of =33% within a 30-day observation period following the index procedure.A Dose-Limiting Toxicity (DLT) is characterized as any device-related adverse event (AE) of Grade 3 or higher, as classified by the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, with the following exceptions:Radiographic-only cerebral edema is excluded.Symptomatic cerebral edema is also excluded if clinical symptoms resolve within 7 days following the initiation of appropriate medical management. | — |
Secondary
| Measure | Time frame |
|---|---|
| The following secondary endpoints will be evaluated to further characterize the safety, efficacy, and patient-centered outcomes associated with Yttrium-90 (Y90) microsphere treatment:Safety AssessmentsIncidence of Adverse Events (AEs): Frequency, severity, causality, and duration of all AEs occurring during the follow-up periodRadiation-Related NeurotoxicityIncidence of Serious Adverse Events (SAEs)Procedure-Related AEsDevice-Related AEsEfficacy AssessmentsTumor Response (Overall and Within the Perfused Volume [PV]) Evaluated using RANO 2.0 criteria, including complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).Progression-Free Survival (PFS) Assessed both overall and within the PV region, per RANO 2.0 criteria.Overall Survival (OS)Time to Subsequent Anti-Cancer TherapyPatient-Reported and Functional OutcomesChange in Quality of Life (QoL): Change from baseline using validated instruments:EORTC QLQ-C30 EORTC QLQ-BN20 Change in Neurocognitive Function: Measured using standardized neuropsychological tests:Hopkins Verbal Learning Test-Revised (HVLT-R)Trail Making Test A and B (TMTA and TMTB)Controlled Oral Word Association Test (COWA)Change in Post-Neurological Function: Evaluated using clinical scales:National Institutes of Health Stroke Scale (NIHSS)Modified Rankin Scale (mRS)Dosimetry and Correlative AnalysisRelationship Between Absorbed Dose to PV and Clinical Outcomes: Exploratory analysis of the relationship between the radiation dose delivered to the PV and observed safety and efficacy endpoints. | — |
Countries
France, Germany, Netherlands, Spain, United States
Contacts
Public ContactY Lambrechts
Boston Scientific
Outcome results
None listed