Poster Presentation Asia Pacific Neuroendocrine Tumour Society 2018

AGITG NABNEC:  A Randomised Phase II Study of Nab-Paclitaxel In Combination With Carboplatin As First Line Treatment Of Gastrointestinal Neuroendocrine Carcinomas (#104)

Lorraine Chantrill 1 , David Ransom 2 , Nick Pavlakis 3 , Adnan Nagrial 4 , Katrin Sjoquist 5 6 , Lara Lipton 7 , Inger Olesen 8 , Ben Markman 9 , James Lynam 10 , Craig Underhill 11 , Abhishek Joshi 12 , Chris Karapetis 13 , Thomas Van Hagen 14 , Louise Wigston 15 , Mustafa Khasraw 16
  1. The Kinghorn Cancer Centre, St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia
  2. Fiona Stanley Hospital, Perth, WA, Australia
  3. Medical Oncology, Northern Cancer Institute, St Leonards, NSW, Australia
  4. Crown Princess Mary Cancer Centre, Westmead, NSW, Australia
  5. Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
  6. Medical Oncology, St George Hospital, Kogarah, NSW, Australia
  7. Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  8. Medical Oncology, University Hospital Geelong, Geelong, VIC, Australia
  9. Medical Oncology, Monash Medical Centre, Moorabbin, VIC, Australia
  10. Medical Oncology, Calvary Mater Newcastle Hospital, Newcastle, NSW, Australia
  11. Border Medical Oncology, Albury, NSW, Australia
  12. Medical Oncology, The Townsville Hospital, Townsville, QLD, Australia
  13. Medical Oncology, Flinders Medical Centre, Adelaide, SA, Australia
  14. Medical Oncology, St John of God Hospital, Subiaco, WA, Australia
  15. Medical Oncology, Royal Hobart Hospital, Hobart, TAS, Australia
  16. Medical Oncology, Royal North Shore Hospital, Sydney, NSW, Australia

Background: Neuroendocrine carcinomas (NEC WHO grade 3) are rare aggressive cancers. There are no randomised trials to date to establish standard therapy for advanced gastrointestinal (GI) NECs. 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,DNA methylation profile; 2) correlation of 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) to early response and other clinical endpoints. SAMPLE SIZE: 70 patients 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 non-resectable GI-NEC (includes small cell and large cell NEC). TREATMENT: Randomisation 2:1 to Arm A nab-paclitaxel 100 mg/m2 on Day (D) 1 weekly and carboplatin AUC=5 on D1, 3 weekly; and Arm B IV etoposide 100mg/m2 on D1-3, and carboplatin AUC=5 on D1, 3 weekly 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 has so far enrolled 17 patients at 15 sites in Australia. ANZCTR # 12616000958482