822P - A phase I dose escalation study investigating dovitinib and everolmus in combination in metastatic clear cell renal cancer patients who have previou...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Cytotoxic agents
Renal Cell Cancer
Biological therapy
Presenter Thomas Powles
Authors T.B. Powles1, R.J. Jones2, S. Crabb3, S. Sarker4, E. Boleti5, J. Shamash4, N. Sarwar6, S. Chowdhury7
  • 1Department Of Medical Oncology, Barts Cancer Insititute, London/UK
  • 2Medical Oncology, Beatson West of Scotland Cancer Centre Gartnavel General Hospital, G12 0YN - Glasgow/UK
  • 3Oncology, Southampton University, London/UK
  • 4Qmul, Barts Cancer Insititute, London/UK
  • 5Oncology, Royal Free Hospital, London/UK
  • 6Medical Oncology, Barts Cancer Insititute, London/UK
  • 7Department Of Medical Oncology, Guys and St Thomas Hospital, London/UK



Both dovitinib and everolimus are agents used, or under investigation in patients with renal cancer refractory to VEGF targeted therapy. It is potentially attractive to use these agents in combination in patients with VEGF TKI refractory disease. Together they target mTOR, VEGF and FGF-2. The purpose of this study is to establish a dose for this combination to take forward in randomised trials.


This phase I study (EUDRACT 2010-021250-19) followed a classic dose escalation 3 + 3 designed. Sequential patients with metastatic clear cell renal cancer, who had previously failed VEGF tyrosine kinase inhibitors were included. Patients received fixed doses of drug in each escalating cohort (maximum n = 6) until dose limiting toxicity (DLT) was reached. DLT included grade 3 toxicity during the first 6 weeks of therapy. If 2 episodes of grade 3 or more toxicity occurred in a specific cohort the DLT cohort had been reached. The study has appropriate ethical approval. Assement of response and progression free survival was by RECIST v1.1


Patients were entered into 2 cohorts before DLT occurred (cohort 0: dovitinib 200 mg/everolimus 5mg [n = 6]; cohort 1: dovitinib 300 mg/everolimus 5mg [n = 3]) . DLT in cohort 1 included grade 3 fatigue (2/3) after 2 and 3 week of therapy. In cohort 0 the following toxicity was identified: Lethargy grade 2 3/6 and 3 1/6; Diarrhoea Grade 2 2/6 and 3 0/6 mucositis; grade 2 0/6 and 3 0/6; nausea/vomiting grade 2 0/6 and 3 1/6, pulmonary fibrosis grade 2 1/6 3 0/6 . Grade 3 toxicity after the first 6 weeks of therapy included pulmonary fibrosis 1/6, lipid abnormalities 2/6. Overall 1 patient (11%) had a partial response to therapy. Of the 5 patients who did not stop therapy during the first 6 weeks due to toxicity, 3 continued for 6 months or more without progression.


The maximum tolerable dose for this combination was dovitinib 200mg and everolimus 5mg. This dose is being taken forward in an expansion cohort which will explore efficacy.


T.B. Powles: Novarits Has supplied an educational grant for this project. Advisroy role for Novratis.

S. Chowdhury: Advisory role.

All other authors have declared no conflicts of interest.