A Phase I study of pevonedistat plus capecitabine plus oxaliplatin in patients with advanced gastric cancer refractory to platinum (NCCH-1811)

Abstract

Based on synergistic anti-tumor effects between blockades of NEDD8 activating enzyme and a platinum in preclinical studies, this Phase I study is designed to investigate the safety and tolerability of pevonedistat in combination with capecitabine plus oxaliplatin as third-line or later treatment in patients with unresectable advanced/recurrent gastric cancer who were previously treated with fluoropyrimidines and platinum (cisplatin or oxaliplatin) as the first-line treatment and paclitaxel (including nab-paclitaxel) as the second-line treatment. The aim of this trial is to determine the recommended dose of pevonedistat and to see its pharmacokinetics in combination with capecitabine plus oxaliplatin in the dose-finding part and explore its efficacy and safety in the expansion part. Trial registration number: jRCT2031190020 (jRCTs: the Japan Registry of Clinical Trials). Lay abstract A Phase I study of pevonedistat plus capecitabine plus oxaliplatin (CapeOX) (NCCH-1811) is designed to investigate the safety and tolerability of pevonedistat in combination with CapeOX as third-line or later treatment in patients with unresectable advanced/recurrent gastric cancer who were previously treated with fluoropyrimidines and platinum (cisplatin or oxaliplatin) as the first-line treatment and paclitaxel (including nab-paclitaxel) as the second-line treatment. The aim is to determine the recommended dose of pevonedistat and to see its pharmacokinetics in combination with CapeOX in the dose finding part and explore its efficacy and safety in the expansion part.