Anti-PD 1 Brain Collaboration + Radiotherapy Extension Study

The ABC-X study, a multicentre investigator-initiated trial sponsored by Melanoma Institute Australia, is a phase II trial, randomised and open label of ipilimumab and nivolumab with concurrent intracranial stereotactic radiotherapy versus ipilimumab and nivolumab alone in patients with melanoma brain metastases. Clinical Trials.gov Registry: NCT03340129

abc-x

Background

Prognosis from melanoma brain metastasis is poor with a median overall survival of 2.8 to 4 months.1,2,3

Nivolumab combined with ipilimumab is active in melanoma brain metastases, with intracranial response rates >55% and durable survival in treatment naïve patients (pts).4

Stereotactic radiosurgery (SRS) and surgery are highly effective local therapies for the individual metastasis5. Surgery and SRS have no proven impact on the risk of developing further melanoma brain metastases, or survival (except in patients with isolated mono or oligo-metastatic brain disease).6,7

The ABC-X seeks to determine if the addition of SRS, to combination immunotherapy with nivolumab and ipilimumab, results in improved intracranial outcomes.

Study Design

Key inclusion criteria

•  ≥ 1 melanoma brain met
•  At least 1 brain lesion ≥ 5mm & all lesions ≤ 40mm
•  Asymptomatic from brain metastases

Sites and contacts

The ABC-X Clinical Trial is being run out of 7 sites in Australia across 4 states, and 1 international site in Norway. The contact details for each location are below.

NSW

Calvary Mater Newcastle (Newcastle, NSW)
T: (02) 4014 3285

Melanoma Institute Australia (Sydney, NSW)
E: Maria.Gonzalez@melanoma.org.au
T: (02) 9911 7300

Westmead Hospital (Sydney, NSW)
E: wslhd-swron-cru@health.nsw.gov.au
T: (02) 8890 5200

Victoria

Alfred Health (Melbourne, VIC)
E: j.andrew@alfred.org.au
T: (03) 9076 0994

Peter Macallum Cancer Centre (Melbourne, VIC)
E: clinicaltrials.enquiries@petermac.org
T: (03) 8559 5000

Queensland

Princess Alexandra Hospital (Brisbane, QLD)
T: (07) 3176 7578

South Australia

Royal Adelaide Hospital (Adelaide, SA)
E: Healthrahcancerclinicaltrials@sa.gov.au

Norway

Oslo University Hospital (Oslo, Norway)

References

  1. Davies, MA, Liu, P, McIntyre, S. et. al. 2011. Prognostic Factors for Survival in Melanoma Patients With Brain Metastases. Cancer 117(8) 1687-1696.
  2. Falchook, GS, Long, GV, Kurzrock, R. et. al. 2012. Dabrafenib in patients with melanoma, untreated brain metastases, & other solid tumours:a phase 1 dose-escalation trial. Lancet 379(9829): 1893-1901
  3. Long, GV, Trefzer, U, Davies, MA. et. al. 2012. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain: a multicentre, open-label, phase 2 trial. Lancet Oncology 13(11) 1087-1095.
  4. Long GV, Atkinson V, Lo S, et. al. 2018. Combination nivolumab & ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol 19 672.
  5. Bernard ME, Wegner RE, Reineman K, et. al. 2012. Linear accelerator based stereotactic radiosurgery for melanoma brain metastases. J Can Res Ther 8 215-21.
  6. Andrews DW, Scott CB, Sperduto PW, et. al. 2004. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. 363(9422) 1665–1672.
  7. Patchell RA, Tibbs PA, Walsh JW, et. al. 1990. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322(8) 494–500.