A28: RADVAN: a randomised double blind phase 2 trial of whole brain radiotherapy with or without vandetanib in metastatic melanoma with brain metastases (ISRCTN20253034)

Avinash Gupta1,Adelyn Wise6,Matthew Goff6,Linda Collins6,Finn Tysoe1,Sharon Love5,Corran Roberts5,Jenny Nobes8,James Lester3,Ernie Marshall2,Carie Corner4,Mark Middleton1,7

1Oxford University Hospitals NHS Trust, Oxford, UK,2Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK,3Weston Park Hospital, Sheffield, UK,4Mount Vernon Cancer Centre, Northwood, UK,5Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, University of Oxford, Oxford, UK,6Oncology Clinical Trials Office, University of Oxford, Oxford, UK,7NIHR Oxford Biomedical Research Centre, Oxford, UK,8Norfolk and Norwich University and Hospitals NHS Foundation Trust, Norwich, UK

Presenting date: Monday 2 November
Presenting time: 13.10-14.00

Background

The clinical incidence of brain metastases in patients with malignant melanoma ranges from 6% to 43%, and brain metastases contribute to death in >95% of cases. Until recently most patients were treated with whole brain radiotherapy (WBRT) with palliative intent and limited effectiveness. Vandetanib is an inhibitor of VEGF, EGF and RET receptor tyrosine kinases, and a potent radiosensitiser.

Method

Eligible patients with melanoma brain metastases were randomised (1:1) to radiotherapy with vandetanib or placebo. Patients received three weeks of either vandetanib 100mg once daily or placebo, starting 4 days (+/- 1 day) before WBRT (30 Gy in 10 fractions). The main study was preceded by a safety run-in phase with 6 patients to confirm regime tolerability. The main aim was to assess efficacy of vandetanib using the primary outcome of progression free survival in the brain (PFS brain) with secondary aims including safety and tolerability.

 

Results

From 71 patients screened, 6 patients were recruited to the safety run-in and a further 18 to the randomised phase which was then closed due to lack of accrual. At closure, in the randomised phase median PFS brain was 3.25 months 95%CI(1.0-5.6) in those randomised to vandetanib compared to 2.50 months 95%CI(0.2-4.8) in the placebo arm (p=0.339 Tarone-Ware test). There were 5 serious adverse events (SAEs) experienced by 5 patients in the arm randomised to vandetanib and 2 SAEs by 2 patients randomised to placebo.

 

Conclusion

The combination of WBRT plus vandetanib was found to be well tolerated in this patient population. Although median PFS brain was increased with the combination, this was not statistically significant due the lack of accrual.  Study recruitment proved challenging due to the increased treatment options in this group of patients.