FRONTIER: A Feasibility Study to Evaluate the Safety of the TheraSphere Glioblastoma (GBM) Device in Patients With Recurrent GBM
Study Details
Study Description
Brief Summary
The FRONTIER Study is a prospective, interventional, single-arm, multi-center, study to assess the safety and technical feasibility of TheraSphere GBM in patients with recurrent GBM.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
Glioblastoma (GBM) is a highly aggressive brain cancer with a grave prognosis, resulting in <7% of patients surviving to five years post-diagnosis. External beam radiotherapy is currently a mainstay treatment for GBM; however, the dose delivered is limited by side effects. The targeted radiotherapy of the TheraSphere GBM Y-90 Glass Microsphere System (TheraSphere GBM) has promising potential to provide GBM patients with reduced side effects compared to external beam radiotherapy as well as a more effective treatment for this catastrophic disease.
The TheraSphere GBM device utilized in the FRONTIER trial is an yttrium-90 (Y-90) glass microsphere therapy for selective internal radiation therapy (endovascular radiotherapy) in recurrent GBM patients as a neoadjuvant to surgery. The TheraSphere GBM treatment utilizes intra-arterial delivery and takes advantage of blood flow and direct tumor delivery. Treatment can be delivered by specific placement of a catheter close to the tumor through known angiographic techniques currently utilized by neuro-endovascular or interventional radiology physicians. Angiographic evaluation prior to treatment allows identification of tumor feeding arteries and definition of the treatment volume. TheraSphere GBM could achieve a high tumor response rate based on delivery of a tumor absorbed dose that is not currently possible with EBRT.
In consideration of the potential benefit of a more localized, targeted treatment with a reduced side effect profile compared to other treatment options, and the potential impact on patients' quality of life for this devastating disease, this First-in-Human Early Feasibility Study (EFS) of the TheraSphere GBM Y-90 Glass Microsphere System for the treatment of recurrent GBM is being conducted.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Absorbed dose target of 40 ± 10% Gy |
Device: TheraSphere GBM
Single treatment of TheraSphere GBM device
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The number of grade 3-5 non-hematological toxicities [30 days post index procedure]
- The number of ≥ grade 3 CNS toxicities related to non-target embolization [30 days post index procedure]
- Occurrence of symptomatic brain radiation necrosis requiring medical or surgical intervention and confirmed by pathology [30 days post index procedure]
- The number of Grade 4 neutropenia events persisting for longer than 5 days [30 days post index procedure]
- The number of grade 4 febrile neutropenia [30 days post index procedure]
- The number of grade 4 thrombocytopenia or grade 3 thrombocytopenia with hemorrhage [30 days post index procedure]
Secondary Outcome Measures
- Rate of any treatment-related adverse events and treatment-related serious adverse events (not including predefined Limiting Toxicities) from first patient enrolled through study completion. [Enrollment through 6 months post index procedure]
- Change in post-treatment neurological function as assessed by the National Institute of Health Stroke Scale (NIHSS). [Enrollment through 6 months post index procedure]
The NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment.
- Change in post-treatment neurological function as assessed by the modified Rankin Scale (mRS). [Enrollment through 6 months post index procedure]
The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability on a scale from 0 (no symptoms at all) to 6 (death).
- Technical Success/Feasibility of TheraSphere GBM-- ability to deliver the target absorbed dose (+/- 20%) to the perfused volume for all patients treated with the device. Assessed from pre-screening through post-device delivery PET-CT/MRI. [Pre-screening through post-device delivery PET-CT/MRI.]
- Objective Response Rate* (ORR) from first patient enrolled through study completion [Enrollment through 6 months post index procedure]
- Progression Free Survival* (PFS) from first patient enrolled through study completion [Enrollment through 6 months post index procedure]
- Overall Survival (OS) from first patient enrolled through study completion [Enrollment through 6 months post index procedure]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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 tumor progression/recurrence with measurable disease (≥ 1 cm to ≤ 5cm bidirectional diameters) by contrast-enhancement on MRI, according to RANO criteria
-
Prior surgery and treatment with combination of radiotherapy and chemotherapy + Tumor Treating Fields (Optune®)
-
Prior cranial radiation dose < 66 Gy
-
WHO performance status ≤ 2
-
The interval since completion of cranial radiotherapy must be > 6 months, unless there is tissue 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 cytotoxic therapy until presumed date of intervention ≥ 1 cycle or ≥ 2 biological half-lives, i.e.
-
≥ 4 weeks since last dose of temozolomide
-
≥ 6 weeks since last dose of lomustine or other nitrosourea
-
≥ 2 weeks since last dose of a small molecule targeted agent
-
≥ 12 weeks from last dose of last bevacizumab infusion, Tyrosine Kinase Inhibitor, or other anti VEGFR therapy
-
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 registration
-
Have adequate organ and bone marrow function within 14 days prior to registration, as defined below:
-
INR ≤ 1.2 (in absence of anticoagulation)
-
Platelets ≥ 100,000/L
-
Creatinine ≤1.5 mg/dL
-
Absolute Neutrophil Count ≥1.5 x 109/L
-
Hemoglobin ≥9.0 g/dL
-
Have a negative pregnancy test within 14 days prior to registration on study (for FOCBP, female of child-bearing potential)
-
Subject is a male or non-pregnant female. If female of child-bearing potential, and if sexually active must be using, or agree to use, a medically acceptable method of birth control as confirmed by the investigator
-
Angiographic Mapping Inclusion Criteria:
-
Accessible neurovascular anatomy that allows for safe microcatheter placement (single location) to infuse TheraSphere GBM to treat all of the T1 enhancing component of lesion confirmed by neuro-interventional team.
-
Treatment volume is ≤ 150cc in the non-dominant hemisphere and non-eloquent regions as determined by multidisciplinary team. Eloquent regions should be defined as areas of the brain that maintain language, vision, sensory and motor function
Exclusion Criteria:
-
Have bilateral gadolinium enhancing disease, tumor located in the posterior fossa, tumor involving critical subcortical structures (thalamus/hypothalamus, midbrain, brainstem, corticospinal tract, internal capsule, cerebral peduncle), tumor approximating or invading the brainstem and/or optic chiasma, leptomeningeal disease, or extracranial metastatic disease
-
Have received more than 1 course of prior radiotherapy (EBRT)
-
Have received radiosurgery, brachytherapy, or hypofractionated radiotherapy
-
Have received more than 2 systemic treatment protocols (lines of treatment), not including maintenance temozolomide
-
Have received more than 2 surgical GBM-related procedures
-
Have received prior thoracic radiation therapy
-
Are at increased risk of wound dehiscence by the discretion of the investigators (e.g. brain surgery within the last 3 months, poor skin condition, and/or previously infected surgical field or any other condition that is of increased infectious risk in the opinion of the neurosurgeon)
-
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, known to have right-to-left shunts, or severe pulmonary hypertension (pulmonary artery pressure > 90 mmHg)
-
Pulmonary insufficiency (arterial oxygen pressure (Pa,O2) of < 60 mmHg, or oxygen saturation (Sa,O2) of < 90%) as measured by fingertip pulse oximeter
-
Ongoing or active bacterial or viral infection requiring systemic treatment (including HIV)
-
Pneumonitis
-
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, study endpoints or longevity
-
Are currently pregnant or breast feeding (unless patient agrees to stop breastfeeding)
-
Patients with a history of an active other malignancy within 1 year prior to registration. NOTE: Exceptions to this requirement include adequately treated non-melanoma skin cancer or lentigo maligna or carcinoma in situ without evidence of disease, or recurrent glioblastoma
-
Patients with a history of ischemic cerebral disease and/or at risk of cerebral herniation
-
Medical contraindication to undergo contrast-enhanced magnetic resonance imaging (MRI)
-
Known history of hypersensitivity reactions to iodinated and/or gadolinium-based contrast
-
Subject has received any other investigational agents within 4 weeks of treatment, or is currently participating, or plans to participate in, another
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California San Francisco | San Francisco | California | United States | 94143 |
| 2 | Mayo Jacksonville | Jacksonville | Florida | United States | 32224 |
| 3 | Northwestern Univerity | Chicago | Illinois | United States | 60611 |
| 4 | Johns Hopkins Interventional Radiology Center | Baltimore | Maryland | United States | 21287 |
| 5 | Lenox Hill Hospital | New York | New York | United States | 10075 |
Sponsors and Collaborators
- Boston Scientific Corporation
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- S2478