A new treatment combination for melanoma brain metastases

Melanoma that spreads to the brain occurs in more than a third of patients with an advanced melanoma diagnosis. Once melanoma metastasises in the brain, patients often have a poor prognosis and a short life expectancy, although advances in treatment – including those pioneered by Australian researchers – are providing hope.

The BETTER clinical trial is testing a new treatment combination that aims to improve the care, treatment, and quality of life for patients with melanoma brain metastases.

The trial will evaluate the safety, tolerability and efficacy of combining the immunotherapy drugs Nivolumab and Ipilimumab with Bevacizumab and targeted radiotherapy in patients with symptomatic melanoma brain metastases.

As well as aiming to extend the patient’s life, this combination treatment may also improve quality of life by reducing the need for immune-suppressing steroids that have many side-effects, and this combination may also lessen the chance of developing radionecrosis (localised areas of brain tissue damage following high dose radiation) which can be induced by high-dose radiation therapy.

Trial funding

The BETTER trial was made possible thanks to the Australian Skin Cancer Foundation’s (ASCF’s) fundraising efforts. Through the ASCF’s first Mission Melanoma campaign, $100,000 was donated in August 2022 to start the trial. ASCF’s second Mission Melanoma campaign raised a further $110,000 for the trial, which was donated in February 2023. 

If the initial trial is successful and further funding can be raised, Melanoma and Skin Cancer Trials hopes to expand the study into a larger trial.

Additional funding will enable more patients, hospital sites and investigators from Australia and overseas to join the trial. A funding boost will also support the trial to publish the robust evidence required to update treatment guidelines with this new treatment combination for patients with symptomatic melanoma brain metastases.


To participate in the BETTER trial, participants must be aged 18 years or older, have been diagnosed with melanoma, and have symptomatic brain metastases or are currently on corticosteroid therapy for brain metastases. Participants must have a life expectancy of more than three months, have had no previous radiotherapy to the brain and are considered not suitable for surgical treatment.

Additional inclusion and exclusion criteria apply.

What's involved?

Phase 1
Participants will receive 2-4 cycles of Bevacizumab in combination with ipilimumab + nivolumab + hypofractionated stereotactic radiotherapy. The primary objective of phase 1 is to assess the safety and tolerability of combination immunotherapy in melanoma brain metastases patients. Participant reaction to the dose of Bevacizumab will be closely monitored, and dose of Bevacizumab may be reduced if necessary, to ensure any potential side effects are minimised. If evaluation after completion of phase 1 confirms the safety and tolerability of the study treatment, the study will proceed to phase 2.

Phase 2
Phase 2 will assess the intracranial (within the skull) clinical benefit of treatment. This includes how effective the combination immunotherapy treatment is at reducing brain metastases, and the level of response observed.

Why is the BETTER trial important?

Patients with symptomatic melanoma brain metastases are usually excluded from clinical trials and this condition is poorly represented in clinical research due to its severity and complexity.

The BETTER trial gives these patients the opportunity to try a new combination treatment that could extend and improve their quality of life.

The results from the BETTER trial will inform treatment guidelines for patients with symptomatic melanoma brain metastases and further medical knowledge for this condition.

BETTER trial team

  • A/Prof Tim Wei Wang – Study Chair, Westmead Hospital and University of Sydney
  • Dr Malaka Ameratunga – Study Chair, Alfred Hospital and Monash University
  • Prof Mark Shackleton, Alfred Hospital and Monash University

Trial sites planned to open for recruitment

  • Westmead Hospital, Sydney
  • The Alfred Hospital, Melbourne

Contact and more information

BETTER trial news

To contact the BETTER clinical trial email

BETTER clinical trial provisional Registration ID: NCT06163820

For information on how to participate in a clinical trial, click here.