Study design
ICH, cancers, Cancer
CANCERS, TUMOURS, DISEASE, BONE METASTASIS, WEST, EVENTS, CANCER
We conducted a phase II double-blind randomised multicentre study from 2012 to 2015. Trial participants were randomised to receive an aromatase inhibitor (AI) plus either saracatinib (AZD0530) or matching placebo tablets. The saracatinib dose was 175 mg orally once daily, administered with or without food. Participants were enrolled into one of two strata. These were either (i) “AI-sensitive/naïve” who were women deemed to have potentially AI-sensitive tumours, or (ii) “prior-AI” who were a group of women whose cancers had already progressed on an AI, but for whom the treating clinician felt there was likely still some endocrine sensitivity (full eligibility outlined below). The “AI-sensitive/naïve” group were appropriate for a non-steroidal AI and received anastrozole 1 mg daily, plus either saracatinib (AZD0530) or placebo. The “prior-AI” group were appropriate for treatment with a steroidal AI and received exemestane 25 mg daily, plus either saracatinib (AZD0530) or placebo. Of note, selective oestrogen receptor downregulators, such as fulvestrant, were not routinely available at the time this trial was conducted.There were twenty registering centres. Randomisation of patients to a treatment group (1:1 allocation) was via a central telephone system at the SCTRU (Scottish Clinical Trials Research Unit, Public Health Scotland) clinical trials unit in Edinburgh, a partner in CaCTUS (Cancer Clinical Trials Unit Scotland). Treatment group was allocated using a minimisation algorithm including the following factors: AI sensitivity, disease site (bone metastasis alone versus any other site), concurrent bisphosphonate use, performance status and treatment centre.Primary analysis was planned after 110 PFS events occurred, or a minimum of 6 months of follow-up in all patients. The study was registered (ISRCTN23804370), sponsored by the Common Services Agency for the Scottish Health Service (UK), partially funded by AstraZeneca (UK) with infrastructure support from the R&D departments of the NHS in the 4 UK nations (NIHR, CSO, HCRW, HSC PHA), and endorsed by Cancer Research UK’s Clinical Trials Awards & Advisory Committee (CTAAC). It was conducted in accordance with ICH Good Clinical Practice and UK National Research Ethics Committee approval was obtained from the West of Scotland Research Ethics Service.