NCT06163820

Bevacizumab and ICIs + hSRT in Symptomatic Melanoma Brain Metastases

Bevacizumab and Immune chEckpoint Inhibitors Plus Hypofractionated Stereotactic radioTherapy for the Treatment of sympTomatic mElanoma bRain Metastases.

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 46 (estimated)
• Sponsor: Melanoma and Skin Cancer Trials Limited · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

Despite significantly improved clinical outcomes for patients with metastatic melanoma, the subset of patients with symptomatic MBM still fare poorly with treatment. The current standard of care for this group of patients is combined immune checkpoint blockade with ipilimumab and nivolumab, with local treatment with neurosurgery or stereotactic radiotherapy added for larger/more symptomatic lesions. Bevacizumab has demonstrated evidence in the treatment of cerebral radiation necrosis and in a case series, promising symptomatic benefit in this group of patients. With strong empirical evidence of the ability to wean patients from steroids, mechanistically, bevacizumab may augment anti-tumour immunity from immune checkpoint blockade. Bevacizumab will be administered 7 days prior to combination immunotherapy with ipilimumab and nivolumab and then given 28 days later to coincide with the second cycle of ipilimumab and nivolumab and thereafter every 3 weeks. The starting dose will be 7.5mg/kg, given intravenously, for a total of four cycles, and is consistent with the existing literature on the treatment of cerebral radiation necrosis. This trial aims to determine the safety of bevacizumab, in combination with ipilimumab, nivolumab and hSRT, defined as no more than 1/6 patients experiencing a bevacizumab-related SAE in the initial phase of the study.

Conditions

• Melanoma Brain Metastases

Interventions

Type	Name	Description
DRUG	Bevacizumab	Bevacizumab is a humanised monoclonal antibody with molecular weight 167kD that inhibits all isoforms of the vascular endothelial growth factor (VEGF) and is produced from a Chinese hamster ovary mammalian system. It has high specificity for isoform-A and has a half-life of \~21 days.
DRUG	Ipilimumab	Ipilimumab is an immune checkpoint inhibitor (ICI) that targets anti-tumour immunity. Ipilimumab is a recombinant human immunoglobulin monoclonal antibody that binds CTLA4 and blocks the interaction between CD80/86 and CTLA4.
DRUG	Nivolumab	Nivolumab ia an immune checkpoint inhibitor (ICI) that targets anti-tumour immunity. Nivolumab is a fully human monoclonal IgG4 antibody targeting PD-1 which demonstrates activity across a range of tumours.
RADIATION	Hypofractionated stereotactic radiotherapy	Hypofractionated stereotactic radiotherapy (hSRT) will be delivered to previously untreated brain metastases in eligible participants. hSRT will be delivered to all symptomatic brain metastases, all brain metastases \>1 cm and all brain metastases located in eloquent areas of the brain. hSRT will be commenced after the first cycle of nivolumab plus ipilimumab and completed before the second cycle of nivolumab plus ipilimumab. hSRT should be commenced within 1 week from the planning MRI.

Timeline

• Start date: 2025-05-31
• Primary completion: 2026-01-30
• Completion: 2026-01-30
• First posted: 2023-12-11
• Last updated: 2025-05-13

Locations

1 site across 1 country: Australia