Recurrent Glioblastoma, Recurrent Glioblastoma IDH Wildtype
Conditions
Keywords
glioblastoma, SIR-spheres, Selective Internal Radiation Therapy, SIRT, Transarterial Radioembolisation, TARE, radioembolisation
Brief summary
This study is testing a new way of treating brain tumours using tiny radioactive beads called SIR-Spheres® (90Y-labelled Resin Microspheres). These microspheres are placed into the blood vessels that feed the tumour. The treatment gives off radiation inside the tumour to try to stop it from growing. This type of treatment is called Selective Internal Radiation Therapy (SIRT), Transarterial Radioembolisation (TARE), or radioembolisation. It is already an accepted treatment for patients with liver cancer. In this study, we are testing if this treatment can be done safely in the brain and how well it works.
Detailed description
This study is testing a new approach to treat people with the most aggressive type of adult brain tumour, glioblastoma. It will determine whether a treatment called selective internal radiation therapy (SIRT) (also know as Transarterial Radioembolisation (TARE), or radioembolisation) is safe and effective in patients with recurrent or progressive glioblastoma. Small radioactive beads (SIR-Spheres®) are administered directly into the blood vessels that feed the tumour. This aims to selectively damage cancer cells and spare healthy tissue. PRECISE will investigate whether SIRT may reduce the volume of the tumour or slow its growth. Participants will undergo a detailed assessment to confirm they are suitable for the treatment. Those enrolled will have a planning procedure to map the blood vessels supplying the tumour, followed by SIRT treatment. Participants will also have scans and medical follow-ups after the procedure to monitor how they are going and whether the treatment is working. Safety of participants will be closely monitored by a team of specialist doctors. This study may represent the initial step towards a new treatment option for people with gliomas, who currently have very few alternatives once standard treatments have failed.
Interventions
DEVICESIR-Spheres®
Single administration of SIR-Spheres® on Day 1 with optional one-time retreatment if clinically indicated
Sponsors
Olivia Newton-John Cancer Research Institute
Austin Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years at the time of screening 2. Histomolecular diagnosis of IDH-wildtype glioblastoma (as per WHO 2021) 3. Prior treatment with radiotherapy and an alkylating agent 4. Presence of measurable disease on brain MRI, as defined by RANO 2.0 criteria 5. Radiologically confirmed disease progression as per RANO 2.0 criteria 6. Lesion confined to a single focus, with a maximum diameter ≤6 cm, and located in a vascular territory amenable to selective intra-arterial catheterisation as assessed on baseline imaging and confirmed by planning angiography, cone beam CT, and \[99mTc\]Tc-MAA SPECT/CT (where available) 7. Stable neurological status; patients with epilepsy may be included if seizures are controlled on a stable dose of anti-epileptic medication 8. ECOG performance status 0-2 9. Estimated life expectancy of ≥3 months, in the opinion of the investigator 10. Adequate haematologic, renal, hepatic, and coagulation function at screening, defined as: * Haemoglobin ≥9 g/dL * Absolute neutrophil count ≥1.5 x 109/L * Platelet count ≥100 x 109/L * Serum creatinine ≤1.5 x ULN, or creatinine clearance ≥30 mL/min (Cockcroft-Gault formula) * Total bilirubin ≤1.5 x ULN (except patients with known Gilbert's syndrome) * Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤2.5 x ULN * International normalized ratio (INR) ≤1.5 x ULN * Prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5 x ULN 11. Ability to understand and comply with study requirements and provide written informed consent.
Exclusion criteria
1. Multifocal glioma recurrence 2. Tumour located in the posterior fossa or involving/risking critical subcortical structures (e.g. thalamus, hypothalamus, basal ganglia, internal capsule, cerebral peduncle, midbrain, brainstem, or optic pathways) 3. Prior treatment with VEGF inhibitors 4. Prior re-irradiation for progressive or recurrent disease 5. Any local (surgery or radiotherapy) or systemic anti-cancer therapy within 28 days prior to the planned dose of the investigational treatment 6. Concurrent use of any anti-cancer therapies, investigational drugs, or biological agents not specified in the protocol 7. Contraindications to MRI, including but not limited to non-compatible implantable devices or severe claustrophobia 8. Contraindications to catheter-based angiography, including but not limited to known bleeding disorders, significant vascular abnormalities precluding safe access, and severe allergy to contrast agents 9. Pregnancy or breastfeeding. Women of childbearing potential and men with partners of childbearing potential must agree to use effective contraception during the study and for at least 4 months after the last procedure. 10. Any severe or uncontrolled medical condition that, in the investigator's judgement, would pose an unacceptable risk to the patient or interfere with protocol compliance 11. Cognitive or psychiatric conditions that would limit the ability to provide informed consent or adhere to study procedures 12. Known hypersensitivity or allergy to 90Y-resin microspheres or any component of the investigational product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Treatment-related adverse events | From SIR-sphere administration (Day 1) to 30 days post SIR-sphere administration. | Rate of any treatment-related adverse events within the first 30 days after TARE, according to CTCAE, version 6.0. |
| Safety - Severe treatment-related adverse events | From SIR-sphere administration (Day 1) to 30 days post SIR-sphere administration. | Rate of any severe treatment-related adverse events (grade ≥3-5) within the first 30 days after TARE, according to CTCAE version 6.0 |
| 30-day mortality | From SIR-sphere administration (Day 1) to 30 days post SIR-sphere administration. | Rate of all-cause mortality within 30 days following TARE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Technical success of TARE | 6 months after the last patient has been enrolled | Technical success rate, defined as successful selective catheterisation and administration of SIR-Spheres® to the target volume without significant non-target deposition. |
| Confirmation of dose delivery | 6 months after the last patient has been enrolled. | Confirmation of dose delivery to the target volume as assessed by post-treatment PET/CT. |
| Objective response rate (ORR) | 6 months after the last patient has been enrolled | Objective response rate (ORR) according to RANO 2.0 and PET RANO 1.0 criteria. |
| Disease control rate (DCR) | 6 months after the last patient has been enrolled | Disease control rate (DCR) according to RANO 2.0 and PET RANO 1.0 criteria. |
| Clinical and radiographic progression-free survival (PFS) | 6 months after the last patient has been enrolled | Clinical and radiographic progression-free survival (PFS) according to NANO, RANO 2.0 and PET RANO 1.0 criteria. |
| Overall survival (OS) | Up to 6 months after the last patient has been enrolled. | Overall survival (OS) |
| Change from baseline in health-related quality of life measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). | Assessed up to 6 months after enrolment | The EORTC QLQ-C30 consists of multi-item functional and symptom scales transformed to scores ranging from 0 to 100. Higher scores indicate better functioning/global health status on the functional and global health scales, whereas higher scores indicate worse symptom burden on the symptom scales. |
| Change from baseline in brain cancer-specific quality of life measured using the European Organisation for Research and Treatment of Cancer Brain Neoplasm Module (EORTC QLQ-BN20). | Assessed up to 6 months after enrolment | The EORTC QLQ-BN20 comprises symptom scales transformed to scores ranging from 0 to 100, with higher scores indicating greater symptom burden (worse quality of life). |
| Safety following repeat administration of SIR-Spheres® administration | Assessed up to 6 months after enrolment | Rate and severity of treatment-related adverse events in participants who proceed to a second SIR-Spheres® administration compared with participants receiving a single administration. |
Countries
Australia
Outcome results
None listed