NABNEC, a randomised Phase II clinical trial recently funded by the NHMRC and supported by Specialised Therapeutics Australia (STA), is now open to patient recruitment.
Currently sites open for this trial include: Royal North Shore Hospital, Westmead Hospital and Calvary Mater Newcastle Hospital. Sites still to be activated are located in NSW, VIC, QLD, WA and TAS.
This clinical trial is a study of the combination of nab-Paclitaxel with carboplatin compared with carboplatin in combination with etoposide as treatment for gastrointestinal Neuroendocrine Carcinomas (NECs).
Neuroendocrine cancers are rare cancers that can develop in different locations throughout the body, including the gastrointestinal tract and the pancreas, with about 500 new cases per year. NECs that have spread around the body (metastasized) or can’t be removed by surgery are incurable with currently available treatments.
“NABNEC is the first clinical trial in the field of neuroendocrine cancers to receive NHMRC funding,” said Dr Mustafa Khasraw, Principal Investigator NABNEC. “We are excited to receive grant funding to study neuroendocrine cancer on a large scale in a multicentre clinical trial that will potentially shed significant insights into the biology and enhance clinical management practices in NECs”
The currently available chemotherapy for people with NECs can result in responses of rather short duration (with less than 5% of patients having an overall survival of greater than 5 years). The combination of etoposide with platinum has been used in small cell lung cancer. Due to the lack of clinical trial data in NEC, the platinum etoposide combination has been the mainstay of therapy for NEC. This treatment is the standard treatment arm of NABNEC and the experimental arm is with carboplatin and NAB paclitaxel instead of etoposide. NAB Paclitaxel has shown enhanced activity in other cancers. NABNEC aims to answer some of the important questions regarding the best use of chemotherapy in improving patient outcomes in NEC. It is intended to determine which treatment has the most activity against NECs. If successful, this trial may change practice for patients with NECs. Regardless of the clinical outcomes of the study, the extensive tissue and blood analysis built into NABNEC will shed light on the biology and increase our understanding of NECs.
To establish if carboplatin and nab-paclitaxel combination is an effective and tolerable chemotherapy treatment for grade 3 advanced gastrointestinal NECs. To explore translational biologic, molecular and functional imaging endpoints to inform future research and improve outcomes for NEC patients.
Neuroendocrine carcinomas (NEC, WHO grade 3), comprising small cell NEC and large cell NEC, are aggressive rare cancers and are generally rapidly fatal. They arise commonly in the gastrointestinal system. There have been a few retrospective studies but no randomised, prospective controlled trials conducted to establish gold standard chemotherapy for advanced gastrointestinal NECs. Etoposide and carboplatin are historical standard of care by extrapolation from small cell lung cancer trials. Paclitaxel and carboplatin are active in gastrointestinal NECs but there is no data on the role of nab-paclitaxel. This randomised study will determine the role of these therapies in clinical practice and to prospectively study the biology and imaging characteristics of NEC.
Study Design and methods:
NABNEC is non-comparative phase II randomised (2:1) stratified multicentre clinical trial. Patients will be stratified in a 2:1 ratio by study site, Ki-67 (<55 v â‰¥ 55), primary site (pancreatic vs non-pancreatic) and FDG-PET uptake and/or avidity (<10 v >10). The study aims to recruit 70 patients from 20 sites in Australia.
Arm A: Experimental arm. IV nab-paclitaxel 100 mg/m2 on Day 1 every week and IV carboplatin AUC=5 on Day 1 every 3 weeks until disease progression or unmanageable toxicity.
Arm B: Control arm. IV etoposide 100mg/m2 on Days 1-3 every week and IV carboplatin AUC=5 on Day 1 every 3 weeks until disease progression or unmanageable toxicity.