A randomized, multicenter, double-blind, placebo (PBO)-controlled phase III study of paclitaxel (PTX) with or without ramucirumab (IMC-1121B; RAM) in patients (pts) with metastatic gastric adenocarcinoma, refractory to or progressive after first-line therapy with platinum (PLT) and fluoropyrimidine (FP).

Abstract

TPS4139 Background: Vascular endothelial growth factor (VEGF) expression in gastric cancer (GC) is associated with more aggressive clinical disease. VEGF expression in resected GC is associated with tumor recurrence and shorter survival. Data from Phase 2 and 3 studies suggest that agents targeting the VEGF pathway improve the efficacy of some chemotherapy regimens in 1st- and 2nd-line treatment of patients with gastric or gastroesophageal carcinomas. RAM, a fully human monoclonal antibody, binds to the VEGF receptor-2 (VEGFR-2), potently blocks the binding of VEGF to VEGFR-2, inhibits VEGF-stimulated activation of VEGFR-2, and neutralizes VEGF-induced mitogenesis of human endothelial cells. Methods: Pts are randomized 1:1 to receive PTX + RAM or PTX + PBO until disease progression or intolerable toxicity (28-day cycle; RAM/PBO 8 mg/kg Days 1, 15; PTX 80 mg/m2 Days 1, 8, 15). Eligibility includes metastatic or locally advanced, unresectable gastric or gastroesophageal junction adenocarcinoma; prior first-line therapy with any PLT/FP doublet with or without anthracycline; progressive disease during or following first-line therapy; ECOG PS 0-1; bilirubin ≤ 1.5 × upper limit of normal (ULN), transaminases ≤ 3 × ULN for ALAT/ASAT if no liver metastases, < 5 × ULN if liver metastases; creatinine ≤ 1.5 × ULN; absolute neutrophil count ≥ 1.5 × 109/L, hemoglobin ≥ 9 g/dL; platelets ≥ 100 × 109/L. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival, time to progression, best overall response, objective response rate, safety, patient-reported outcome measures, pharmacodynamics, immunogenicity, and pharmacokinetics. This study, powered at 90% to show an increase in OS (mdn: 7 m PTX + PBO, 9.33 m PTX + RAM) at a 1-sided 2.5% significance level, will randomize 663 pts. As of 18 January 2012, approximately 58% of planned pts were randomized. The IDMC reviewed this study 23 June and 01 December 2011 and recommended the study continue unmodified.