Background: Neuroendocrine carcinomas (NEC WHO grade 3) are rare and aggressive cancers. There are no randomised trials to date to establish standard therapy for advanced gastrointestinal (GI) NECs. Extrapolating from small cell lung cancer data, standard practice is to treat GI-NECs with etoposide and carboplatin. Paclitaxel is also active in NECs however there is no data on the role of nab-paclitaxel. NABNEC aims to establish if the carboplatin and nab-paclitaxel combination is an effective and tolerable treatment for advanced GI-NECs and to enhance our understanding of the biology and imaging characteristics of NECs. Methods: Design: Randomised, non-comparative, stratified, multicentre phase 2 trial. Primary endpoint (n=70): objective response rate (RR) by RECIST 1.1 at 6 months. Secondary endpoints: progression free survival, overall survival, adverse events by NCI-CTCAE V4.03 and quality of life (EORTC QLQC30, QLQ-GINET21 questionnaires). Translational endpoints include 1) blood and tissue biomarkers (prognostic and/or predictive) correlated with clinical endpoints including circulating tumour cells, mutation profile (whole exome sequencing), DNA methylation profile; 2) correlation of 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) to early response and other clinical endpoints. Sample Size: 70 patient’s gives 80% power and 95% confidence to rule out a 30% RR in favour of a clinically relevant RR of 50% at 6 months. Population: Adults with advanced or metastatic non-resectable GI-NEC (includes small cell and large cell NEC). Treatment: Randomisation 2:1 to Arm A IV nab-paclitaxel 100 mg/m2 on Day (D) 1 weekly and IV carboplatin AUC=5 on D1, 3 weekly; and Arm B IV etoposide 100mg/m2 on D1-3, and IV carboplatin AUC=5 on D1, 3 weekly to continue until disease progression or unacceptable toxicity. Assessments: ⁶⁸Ga Octreotate PET at baseline, CT scan at baseline and every 9 weeks, FDG PET at baseline, 9 weeks then every 18 weeks and QOL questionnaires every 9 weeks until disease progression. NABNEC is enrolling patients at 12/20 planned study sites in Australia and New Zealand. ANZCTR #. Clinical trial information: 12616000958482.