Neo-CREATE: Neoadjuvant immune-chemo-radiotherapy in operable oesophageal and gastro-oesophageal junction adenocarcinoma cancers with carboplatin paclitaxel radiotherapy and avelumab

Oesophago-gastric (OG) cancers are a significant global health burden, representing the 8^th most commonly diagnosed cancer. The incidence rates of distal oesophageal and gastro-oesophageal junction cancers are rising in western countries.

The purpose of this study is to assess the safety of adding avelumab (anti-PDL1) to chemo-radiation using two standard chemotherapy drugs, carboplatin, and paclitaxel (CROSS protocol), before surgery in patients with cancers of the oesophagus or gastro-oesophageal junction.

Neo-CREATE is an investigator initiated single arm, multi-centre phase II trial evaluating the safety and preliminary efficacy of avelumab, an anti-PD-L1 monoclonal antibody, with neoadjuvant carboplatin-paclitaxel CRT for patients with operable OG adenocarcinoma. Primary objective of Neo-CREATE is pCR rate and secondary objectives include safety, PFS, OS, QoL and correlative biomarker analysis. The recruitment target is 47 patients over 3-year period. All patients will be analyzed as per ITT regardless of whether they undergo surgery or not. The trial has a run-in phase of 10 patients to evaluate feasibility and safety and a planned futility analysis after 15 patients have undergone surgery. The trial will be stopped for further recruitment if > 2 of the 1st ten patients cannot undergo surgery or have significant perioperative complications due to avelumab-related toxicities.