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TPS4145 Background: Surgery forms the mainstay of curative treatment for oesophageal and gastro-oesophageal junction adenocarcinoma (OAC). Preoperative chemotherapy (CTX) with or without concurrent radiotherapy (CRT) have resulted in modest improvements in outcome. Patients who demonstrate a histological response in the resected specimen following pre-operative therapy (CTX or CRT) have consistently better survival than non-responders. Recent data suggests that early metabolic response, assessed by FDG-PET scan performed 14+/-1 days after the start of CTX compared with a baseline PET scan, is predictive of a histological response and improved survival. Increasing the proportion of responders to pre-operative therapy remains one of the major challenges facing patients with localised OAC. Methods: 150 patients with resectable adenocarcinona of the oesophagus or GOJ will be registered and given 1 cycle of cisplatin and 5FU (CF). Patients will undergo a series of baseline tests including endoscopy, endoscopic ultrasound and 18FDG-PET. At Day 15 of the initial CF cycle the PET will be repeated. Patients with a PET response (≥ 35% reduction in SUVmax) to initial treatment will continue with CF as standard treatment prior to surgery. PET non-responders (< 35% reduction in SUVmax) will be randomized equally to receive either docetaxel, cisplatin and 5FU (DCF) or DCF plus radiatiotherapy. Following completion of the preoperative chemotherapy /chemoradiotherapy patients will have their cancer surgically removed. The primary end point is major histological response (

TPS4681 Background: Treatment of RCC has improved due to better understanding of its biology. New targeted therapies have improved time to progression and overall survival but the optimal sequencing of agents is unknown. Currently drugs are given sequentially, usually starting with sunitinib and often followed by an mTOR inhibitor or another VEGFR-targeted therapy, but resistance to both drugs eventually occurs probably due to host adaptive responses. We hypothesize that resistance might be delayed by planned alternation of treatments. Methods: EVERSUN is a single-arm, two-stage, multicenter, phase II clinical trial aiming to determine the activity and safety of an alternating regimen of two therapies with different targets (sunitinib and everolimus) in patients with advanced RCC. Key eligibility criteria: RCC with a clear cell component; metastatic or locally advanced disease not suitable for resection; ECOG performance status 0-1; low or intermediate MSKCC prognostic score. The primary endpoint is the status of being alive and progression-free (RECIST 1.1) 6 months after registration. Target accrual of 55 subjects gives 95% power and 95% confidence to distinguish between 6-month progression free survival rates of 64% or lower vs 84% or higher using a Simon 2-stage minimax design. The criteria for further evaluation come from the pivotal trial of single agent sunitinib as first line therapy for RCC, in which the 6-month progression free survival rate was 74%. Trial treatment is administered in 12-week (wk) cycles consisting of 4 wks of sunitinib (50 mg daily) followed by 2 wks rest, followed by 5 wks of everolimus (10 mg daily) followed by 1 wk rest. Disease progression is interpreted as failure of the most recent drug taken. Participants who stop one drug because of toxicity or disease progression, on or before the 6 month assessment, will continue the other drug until subsequent progression or prohibitive toxicity on the second drug. EVERSUN is an ANZUP Cancer Trials Group Ltd. trial coordinated by the NHMRC Clinical Trials Centre. Accrual commenced in September 2010 with 38/55 participants recruited as of the 31-Jan-12 from 17 Australian sites (ACTRN12609000643279).

Stephen J. Clarke *, Sonia Yip , Chris Brown , Guy A. van Hazel , David T. Ransom , David Goldstein , G. Mark Jeffrey , Niall C. Tebbutt , Martin Buck , Raymond M. Lowenthal , Amy Boland , Val Gebski , John Zalcberg , R. John Simes , on behalf of the Australasian Gastro-Intestinal Trials Group a Department of Medicine, Concord Hospital, Concord, Sydney, Australia b National Health and Medical Research Council (NHMRC) Clinical Trials Centre, University of Sydney, Sydney, Australia c School of Medicine and Pharmacology, University of Western Australia, Perth, Australia d St. John of God Hospital, Perth, Australia e Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia f Oncology Service, Christchurch Hospital, Christchurch, New Zealand g Austin Health, Melbourne, Australia h Sir Charles Gairdner Hospital, Perth, Australia i Royal Hobart Hospital and University of Tasmania, Hobart, Australia j Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Australia