A Feasibility Study to Evaluate the Safety of the TheraSphere Glioblastoma (GBM) Device in Patients With Recurrent GBM

Glioblastoma Multiforme Clinical Trial

— FRONTIER  

Official title:

FRONTIER: A Feasibility Study to Evaluate the Safety of the TheRaSphere GliOblastoma (GBM) Device iN PaTIEnts With Recurrent GBM

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05303467
• Other study ID #: S2478
• Status: Recruiting
• Phase: Early Phase 1
• Start date: July 30, 2022
• Est. completion date: June 1, 2025

Study information

• Verified date: April 2024
• Source: Boston Scientific Corporation
• Contact: Sally Linda
• Phone: 952-201-3102
• Email: sally.linda[@]bsci.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 (EBRT) 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: June 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subject is 18 years or older and has signed and dated the trial informed consent form (ICF)

2. Life expectancy = 12 weeks

3. Subject is willing and able to comply with the trial testing, procedures, and follow-up schedule

4. History of a histologically confirmed diagnosis of glioblastoma per 2021 WHO criteria

5. 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

6. Prior surgery and treatment with combination of radiotherapy and chemotherapy ± Tumor Treating Fields (Optune®)

7. Prior cranial radiation dose < 66 Gy

8. WHO performance status = 2

9. 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

10. Interval since last cytotoxic therapy until presumed date of intervention = 1 cycle or = 2 biological half-lives, i.e.

1. = 4 weeks since last dose of temozolomide

2. = 6 weeks since last dose of lomustine or other nitrosourea

3. = 2 weeks since last dose of a small molecule targeted agent (Tyrosine Kinase Inhibitor or similar)

4. = 12 weeks from last dose of last intravenous bevacizumab infusion, or other antibody-based VEGF therapy

11. 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

12. Have adequate organ and bone marrow function within 14 days prior to registration, as

defined below:

1. INR = 1.2 (in absence of anticoagulation)

2. Platelets = 100,000/L

3. Creatinine =1.5 mg/dL

4. Absolute Neutrophil Count =1.5 x 10^9/L

5. Hemoglobin =9.0 g/dL

13. Have a negative pregnancy test within 14 days prior to registration on study (for FOCBP, female of child-bearing potential)

14. 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

15. Angiographic Mapping Inclusion Criteria:

1. Accessible neurovascular anatomy that allows for safe microcatheter placement (up to two locations) to infuse TheraSphere GBM to treat all of the T1 enhancing component of lesion confirmed by neuro-interventional team.

2. Total 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:

1. 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

2. Have received more than 1 course of prior cranial radiotherapy (EBRT)

3. Have received radiosurgery, brachytherapy, or hypofractionated radiotherapy

4. Have received more than 2 systemic treatment protocols (lines of treatment), not including maintenance temozolomide

5. Have received prior intra-arterial cerebral infusion therapy

6. Have received more than 2 surgical GBM-related procedures

7. Have received prior thoracic radiation therapy

8. 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)

9. Have uncontrolled epilepsy

10. Have severe and/or insufficiently controlled intercurrent illness; patients with the

following are not eligible:

1. Hypertension grade 3 or higher without adequate control on medications

2. Symptomatic or unstable cardiac disease, known to have right-to-left shunts, or severe pulmonary hypertension (pulmonary artery pressure > 90 mmHg)

3. Pulmonary insufficiency (arterial oxygen pressure (Pa,O2) of < 60 mmHg, or oxygen saturation (Sa,O2) of < 90%) as measured by fingertip pulse oximeter

4. Ongoing or active bacterial or viral infection requiring systemic treatment (including HIV)

5. Pneumonitis

6. Psychiatric illness/social situations that would limit compliance with study requirements

7. Peripheral Neuropathy = grade 1

8. 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

11. Are currently pregnant or breast feeding (unless patient agrees to stop breastfeeding)

12. 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

13. Patients with a history of ischemic cerebral disease and/or at risk of cerebral herniation

14. Medical contraindication to undergo contrast-enhanced magnetic resonance imaging (MRI)

15. Known history of hypersensitivity reactions to iodinated and/or gadolinium-based contrast

16. Subject has received any other investigational agents within 4 weeks of treatment, or 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)

17. Angiographic Mapping Exclusion Criteria: Patients with significant vascular disease, significant AV shunting, or anatomic tortuosity on MR/CT Angiogram precluding safe or feasible vascular access or an eloquent high-risk vascular distribution of the treatment plan

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme
• Recurrence
• Recurrent Glioblastoma

Intervention

Device:
• TheraSphere GBM
Single treatment of TheraSphere GBM device

Locations

Country	Name	City	State
United States	Johns Hopkins Interventional Radiology Center	Baltimore	Maryland
United States	Northwestern Univerity	Chicago	Illinois
United States	Mayo Jacksonville	Jacksonville	Florida
United States	Lenox Hill Hospital	New York	New York
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Boston Scientific Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of grade 3-5 non-hematological toxicities		30 days post index procedure
Primary	The number of = grade 3 CNS toxicities related to non-target embolization		30 days post index procedure
Primary	Occurrence of symptomatic brain radiation necrosis requiring medical or surgical intervention and confirmed by pathology		30 days post index procedure
Primary	The number of Grade 4 neutropenia events persisting for longer than 5 days		30 days post index procedure
Primary	The number of grade 4 febrile neutropenia		30 days post index procedure
Primary	The number of grade 4 thrombocytopenia or grade 3 thrombocytopenia with hemorrhage		30 days post index procedure
Secondary	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
Secondary	Change in post-treatment neurological function as assessed by the National Institute of Health Stroke Scale (NIHSS).	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.	Enrollment through 6 months post index procedure
Secondary	Change in post-treatment neurological function as assessed by the modified Rankin Scale (mRS).	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).	Enrollment through 6 months post index procedure
Secondary	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.
Secondary	Objective Response Rate* (ORR) from first patient enrolled through study completion		Enrollment through 6 months post index procedure
Secondary	Progression Free Survival* (PFS) from first patient enrolled through study completion		Enrollment through 6 months post index procedure
Secondary	Overall Survival (OS) from first patient enrolled through study completion		Enrollment through 6 months post index procedure