ST03: A randomized trial of perioperative epirubicin, cisplatin plus capecitabine (ECX) with or without bevacizumab (B) in patients (pts) with operable gastric, esophagogastric junction (OGJ), or lower esophageal adenocarcinoma.

Abstract

TPS4156 Background: Perioperative ECX chemotherapy is a standard of care for localised operable gastric/OGJ/lower oesophageal adenocarcinoma (Cunningham, NEJM 2006). In combination with chemotherapy B, a monoclonal antibody targeting VEGF-A, results in improved response rates (RR) and progression free survival in advanced gastric cancer (Ohtsu, JCO 2011). ST03 aims to assess the safety and feasibility (stage I, 200 pts) and efficacy (stage II) of the addition of B to perioperative ECX chemotherapy. Methods: ST03 is a multicentre, open-label, phase II/III randomised trial open at 106 UK centres. Eligibility criteria are histologically proven, untreated, resectable, lower oesophageal, OGJ or gastric adenocarcinoma; age ≥18 years; WHO PS 0-1; and adequate cardiac ejection fraction (EF). Exclusion criteria are TIA/CVA or MI ≤1 year; uncontrolled hypertension; ≥ Grade 2 NYHA heart failure; recent gastrointestinal inflammatory conditions or major surgery/trauma/open biopsy <28d of study entry. Pts receive 3 pre- and 3 postoperative ECX (epirubicin 50 mg/m2 iv D1, cisplatin 60 mg/m2 iv D1 and capecitabine 1250mg/m2/D1-21) +/- B 7.5mg/kg D1 q3wk during chemotherapy, then 6 B q3wk (investigational arm). Surgery is pre-specified and laparoscopic procedures allowed only after quality assurance review. All specimens undergo central pathology review; blood and tissue collection for translational studies is ongoing. Stage I Safety results including cardiac EF have been reported (Okines Ann Oncol 2012). The stage II primary outcome measure is overall survival. Secondary outcome measures are RR, resection rate, disease free survival, toxicity, and QoL. MRI and PET substudies are ongoing. 877 of 1,100 pts have been recruited, accrual expected to complete in Q4 2013. A pilot study within ST03 randomising HER2 positive pts to ECX ± lapatanib (L) opened Q1 2013 and will assess safety, HER2 positivity rate and feasibility in 40 pts randomised between standard ECX and modified ECX+L. Trial sponsored and co-ordinated by the MRC Clinical Trials Unit and funded by Cancer Research UK (CRUK06/025, NCT00450203). Clinical trial information: NCT00450203.