Gupta, A;
Roberts, C;
Tysoe, F;
Goff, M;
Nobes, J;
Lester, J;
Marshall, E;
... Middleton, MR; + view all
(2016)
RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases - results and lessons learnt.
British Journal of Cancer
, 115
(10)
pp. 1193-1200.
10.1038/bjc.2016.318.
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RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases - results and lessons learnt.pdf - Published Version Download (297kB) | Preview |
Abstract
BACKGROUND: Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. METHODS: In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. RESULTS: Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6-5.6) in the vandetanib group and 2.5 months (90% CI: 0.2-4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6-6.3) and 2.5 months (90% CI: 0.2-7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. CONCLUSIONS: The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area.
| Type: | Article |
|---|---|
| Title: | RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases - results and lessons learnt |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/bjc.2016.318 |
| Publisher version: | https://doi.org/10.1038/bjc.2016.318 |
| Language: | English |
| Additional information: | From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| Keywords: | Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Brain, Brain Neoplasms, Combined Modality Therapy, Disease-Free Survival, Double-Blind Method, Female, Humans, Male, Melanoma, Middle Aged, Piperidines, Quinazolines, Radiation-Sensitizing Agents, Radiotherapy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10059963 |
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