Fulvestrant +/- Vandetanib in advanced aromatase inhibitor resistant breast cancer


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Joanna Smith1,Zoe Hudson2,Tracie-Ann Madden1,Angela Casbard1,Laura Butlin1,Terri Kitson1,Mark Beresford3,Peter Barrett-Lee4,Sacha Howell5,David Cameron6,Julia Gee2,Jacinta Abraham4,Kay Wilson4,Bethan Tranter4,Gareth Griffiths7,Lesley Radley8,Robert Jones4
1Centre for Trial Research, Cardiff University,2Cardiff University,3Royal United Hospital Bath,4Velindre Cancer Centre,5The University of Manchester,6The University of Edinburgh,7University of Southampton Clinical Trials Unit,8c/o Centre for Trial Research, Cardiff University

Abstract

Background

Hormone therapy is often the best treatment for patients with ER+ advanced breast cancer. However, over time cells become resistant to therapy via multiple mechanisms, including a ‘signalling’ pathway involving  RET. Research has shown increased activity of this pathway in hormone therapy resistant cancer cells. Vandetanib inhibits RET signalling and has been shown in laboratory studies to prevent the growth of such cells. Combining Vandetanib with hormone therapy may, therefore, delay resistance to endocrine treatment in patients with ER+ breast cancer.

Method

FURVA is a randomised, double blind, placebo-controlled Phase II study of Fulvestrant +/- Vandetanib for postmenopausal, female patients with metastatic breast cancer resistant to aromatase inhibitor therapy. 160 subjects will receive 16 x 4 week cycles of treatment: Fuvestrant 500mg IM Day1, D15, then D1 of every 28 day cycle, plus Vandetanib 300mg po daily (Treatment Arm) or matched placebo (Control Arm). The primary objective is progression-free survival (RECIST v1.1). Secondary objectives include safety and tolerability, objective response rate and clinical benefit (RECIST v1.1), overall survival, time from enrolment to death with those still alive censored at date last seen, and an exploratory translational analysis to determine the influence of RET signalling pathway components expression on Vandetanib activity. Sponsor: Velindre NHS Trust. Funders: CRUK CTAAC, Velindre Charitable Funds, AstraZeneca/NCRN. Other support: ECMC and NIHR CRN.

Results

160 subjects were recruited over 26 months by 04/07/2017, two months ahead of schedule. The subject number target was extended by ≤10%. Closure of the recruitment phase is scheduled approximately 31/08/2017.

Conclusion

We will discuss screening, final recruitment and baseline translational blood and tissue sample data collected thus far, the impact of sample return compliance on the design of the translational study, and the positive and negative aspects of an AZ-NCRN lessons learned exercise and how this could impact on future clinical trial design.