Neuroendocrine carcinomas (NEC WHO grade 3) are aggressive cancers that are rapidly fatal. There have been no randomised trials to date to establish standard therapy for advanced gastrointestinal (GI) NECs. Etoposide and carboplatin are used by extrapolation from small cell lung cancer data. Paclitaxel is also active in NECs but there is no data on the role of nab-paclitaxel. This randomised study aims to establish if carboplatin and nab-paclitaxel combination is an effective and tolerable treatment for advanced GI NECs.
NABNEC has commenced as a randomised phase II multicentre trial enrolling adults with advanced and/or metastatic non-resectable GI NECs. Patients are randomised to: Arm A (n = 47) IV nab-paclitaxel 100 mg/m2 on Day 1 every week and IV carboplatin AUC = 5 on Day 1 every 3 weeks OR: Arm B (n = 23) IV etoposide 100mg/m2on Days 1-3 every 3 weeks and IV carboplatin AUC = 5 on Day 1 every 3 weeks. Treatment will continue until disease progression or unmanageable toxicity. The primary endpoint is objective response rate (RR) by RECIST 1.1. At 6 months, the RR in the intervention group would need to be at least 50% to justify further investigation. A total sample size of 70 patients with a 2:1 randomisation (intervention to control) will have 80% power with 95% confidence to rule out a 30% objective RR in favour of a more clinically relevant RR of 50% at 6 months. Secondary endpoints include progression free survival, overall survival, safety as measured by NCI-CTCAE V4.03, and quality of life using EORTC QLQC30 and QLQ-GINET21 questionnaires. Translational research endpoints include (1) blood and tissue biomarkers (prognostic and/or predictive) correlated with clinical endpoints including (a) circulating tumour cells, (b) mutation profile by whole exome sequencing, (c) DNA methylation profile and (2) utility of 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) imaging as an early predictor of response and association of SUV max with clinical endpoints. NABNEC has opened to recruitment at 9 study sites and is currently enrolling patients. The randomised NABNEC study will run at 20 sites in Australia and New Zealand. ANZCTR # 12616000958482.
Clinical trial identification
AG0215NET/CTC0137 Version 1.1 29 February 2016
Legal entity responsible for the study
Australasian Gastro-Intestinal Trials Group
National Health and Medical Research Council (NHMRC); Specialised Therapeutics Australia PTY Ltd (STA)
M. Khasraw, J. Simes: Funding to Institution from Specialised Therapeutics Australia PTY Ltd. M. Michael: Consulting or Advisory Role: Ipsen; Novartis Pharma KK; travel, accommodations, expenses: Ipsen. All other authors have declared no conflicts of interest.