Title: Clinical trials in renal cancer
Funder: Medical Research Council

Abstract: Kidney or renal cell cancer (RCC) is the 13th commonest cancer diagnosed in the UK. The annual incidence in the UK is approximately 6,200 and rising, with around 2,500 deaths (CRUK figures 2006). Nearly 2 out 3 people diagnosed (62%) are over 65 years old. RCC is more common in men than in women. Approximately 25% of patients have metastatic disease at presentation. The renal team at the MRC CTU currently has 2 active trials in their portfolio. The RE04 trial in advanced RCC patients is closed to accrual but still in active follow-up, while the RE05 (SORCE) trial in the adjuvant treatment setting opened to accrual in July 2007. The standard therapy in the UK for patients with metastatic RCC was, until the recent introduction of targeted agents, single agent interferon-alpha (IFN-alpha) in those fit to tolerate treatment. RE04 is an open-label randomised controlled phase III trial to compare triple combination (IFN-alpha, IL-2 and 5FU) to monotherapy with IFN-alpha in this group of patients. The trial objectives were to assess (i) the value of the triple combination therapy in terms of overall survival time, progression-free survival time and toxicity compared with IFN-alpha alone (ii) the quality of life in patients in both treatment arms during therapy and follow-up and (iii) the health economic implications of using triple therapy compared to the control regimen. The trial closed to accrual in July 2006 having reached its accrual target of 1000 patients (1006 patients were recruited). Preliminary results have been published in abstract and presented in poster form at ASCO 2008. A paper presenting the results has been submitted to a leading medical journal and should be published later in 2009. RE05 (SORCE) is a multi-centre randomised phase III double-blind placebo-controlled study examining the efficacy and tolerability of sorafenib (Nexavar) in patients with resected (total or partial) primary RCC at high or intermediate risk or relapse. Sorafenib, an oral inhibitor of several kinases known to be important in the pathobiology of RCC, has been shown to prolong progression-free survival in advanced RCC and therefore a trial in the adjuvant setting is felt to be both timely and worthwhile. The trial aims to answer two questions. The first question is whether at least one year of treatment with sorafenib increases DFS (disease-free survival) compared with placebo. The second question is about the duration of sorafenib and whether three years of treatment increases DFS compared to one year of treatment. The trial opened in the UK in July 2007 and has a target accrual of 1656 patients over the next 5 years. The first international patient was recruited in February 2009. The countries that are taking part are Belgium, Holland and Italy (through the EORTC), Denmark, France, Spain, Australia and New Zealand. Two ancillary studies are currently taking place in the UK; a translational research programme (TRANSORCE) and a cost-effectiveness study. The translational research programme involves the collection of blood and/or fixed and fresh-frozen tumour (where available) from consenting patients and involves collaborations with the University of Leeds and the Institute of Cancer Research (UK). The cost-effectiveness study involves collaboration with the University of York.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS