Bevacizumab and Immune chEckpoint Inhibitors Plus Hypofractionated Stereotactic radioTherapy for the Treatment of sympTomatic mElanoma bRain Metastases.
Single arm phase I/II trial to evaluate the safety and efficacy of the combination of bevacizumab, with ipilimumab plus nivolumab, and hypofractionated stereotactic radiotherapy (hSRT) in patients with symptomatic melanoma brain metastases (MBM).
• 1\. Histologically (or cytologically) proven metastatic melanoma, with radiologically confirmed brain metastases.
• 2\. Symptomatic from brain metastases at the time of study enrolment, or brain metastases that requires corticosteroids for the management of neurological symptoms.
• 3\. Intracranial lesions amenable to hypofractionated stereotactic radiotherapy. These are defined as all intracranial melanoma lesions greater or equal to 5 mm in diameter, all intracranial lesions that are causing symptoms, and all intracranial lesions located in the eloquent areas of the brain.
• 4\. World Health Organisation (WHO) performance status of 0 - 2
• 5\. At least one brain metastasis has to be symptomatic.
• 6\. Laboratory tests required: Haemoglobin (Hb) ≥ 9.0 g/dL Absolute neutrophil count ≥ 1 x 109/L Platelet count ≥ 100 x 109/L Either: Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) (Patients with isolated hyperbilirubinaemia due to Gilbert's syndrome are allowed.) Or: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x (ULN) unless raised due to tumour in which case up to 5 x ULN is permissible Creatinine clearance ≥ 40 mL/min (Cockcroft-Gault or MDRD are acceptable)
• 7\. Age ≥ 18 years
• 8\. Able to provide informed written consent (signed and dated), attend trial site for study visits and be capable of co-operating with treatment and follow-up