Pilot Radioembolisation Clinical Trial Assessing Safety and Efficacy in Recurrent Glioma

Official title

Pilot Radioembolisation Clinical Trial Assessing Safety and Efficacy in Recurrent Glioma (PRECISE)

Overview

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

• Device SIR-Spheres®
  Single administration of SIR-Spheres® on Day 1 with optional one-time retreatment if clinically indicated

Primary outcome measures

• Safety - Treatment-related adverse events [Time frame: From SIR-sphere administration (Day 1) to 30 days post SIR-sphere administration.]
• Safety - Severe treatment-related adverse events [Time frame: From SIR-sphere administration (Day 1) to 30 days post SIR-sphere administration.]
• 30-day mortality [Time frame: From SIR-sphere administration (Day 1) to 30 days post SIR-sphere administration.]

Secondary outcome measures (9)

• Technical success of TARE [Time frame: 6 months after the last patient has been enrolled]
• Confirmation of dose delivery [Time frame: 6 months after the last patient has been enrolled.]
• Objective response rate (ORR) [Time frame: 6 months after the last patient has been enrolled]
• Disease control rate (DCR) [Time frame: 6 months after the last patient has been enrolled]
• Clinical and radiographic progression-free survival (PFS) [Time frame: 6 months after the last patient has been enrolled]
• Overall survival (OS) [Time frame: Up to 6 months after the last patient has been enrolled.]
• 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). [Time frame: Assessed up to 6 months after enrolment]
• 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). [Time frame: Assessed up to 6 months after enrolment]
• Safety following repeat administration of SIR-Spheres® administration [Time frame: Assessed up to 6 months after enrolment]

Eligibility criteria

Inclusion criteria

• Age ≥18 years at the time of screening
• Histomolecular diagnosis of IDH-wildtype glioblastoma (as per WHO 2021)
• Prior treatment with radiotherapy and an alkylating agent
• Presence of measurable disease on brain MRI, as defined by RANO 2.0 criteria
• Radiologically confirmed disease progression as per RANO 2.0 criteria
• 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)
• Stable neurological status; patients with epilepsy may be included if seizures are controlled on a stable dose of anti-epileptic medication
• ECOG performance status 0-2
• Estimated life expectancy of ≥3 months, in the opinion of the investigator
• 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
• Ability to understand and comply with study requirements and provide written informed consent.

Exclusion criteria

• Multifocal glioma recurrence
• 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)
• Prior treatment with VEGF inhibitors
• Prior re-irradiation for progressive or recurrent disease
• Any local (surgery or radiotherapy) or systemic anti-cancer therapy within 28 days prior to the planned dose of the investigational treatment
• Concurrent use of any anti-cancer therapies, investigational drugs, or biological agents not specified in the protocol
• Contraindications to MRI, including but not limited to non-compatible implantable devices or severe claustrophobia
• 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
• 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.
• 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
• Cognitive or psychiatric conditions that would limit the ability to provide informed consent or adhere to study procedures
• Known hypersensitivity or allergy to 90Y-resin microspheres or any component of the investigational product

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 1 center

• Austin Hospital — Melbourne

Identifiers

NCT: NCT07712770 · ONJ2025-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗