NET-02 trial protocol: a multicentre, randomised, parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (NEC)

Abstract

Introduction: Poorly differentiated (PD), extrapulmonary (EP), neuroendocrine carcinomas (NECs) are rare but aggressive neuroendocrine neoplasms. First-line treatment for advanced disease is an etoposide and platinum-based chemotherapy combination. There is no established second-line treatment for patients with PD-EP-NEC, and this is an area of unmet need.

Methods and analysis: NET-02 is a UK, multicentre, randomised (1:1), parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive PD-EP-NEC. One hundred and two eligible participants will be randomised to receive either nal-IRI/5-FU/folinic acid or docetaxel. The primary objective is to determine the 6-month progression-free survival (PFS) rate. The secondary objectives of this study are to determine PFS, overall survival, objective response rate, toxicity, quality of life and whether neuron-specific enolase is predictive of treatment response. If either treatment is found to have a 6-month PFS rate of at least 25%, that treatment will be considered for a phase III trial. If both treatments meet this target, prespecified selection criteria will be applied to establish which treatment to take forward.

Ethics and dissemination: This study has ethical approval from the Greater Manchester Central Research Ethics Committee (reference no. 18/NW/0031) and clinical trial authorisation from the Medicine and Healthcare Products Regulatory Agency. Results will be published in peer-reviewed journals and uploaded to the European Union Clinical Trials Register.

Trial registration numbers: ISRCTN10996604, NCT03837977, EudraCT Number: 2017-002453-11.

Keywords: docetaxel; liposomal irinotecan; neuroendocrine carcinoma; randomised; single-stage.

Conflict of interest statement

Competing interests: JW reports grants and personal fees from AstraZeneca, grants and personal fees from SanofiGenzyme, personal fees and non-financial support from Celgene, personal fees from Eisai, personal fees and non-financial support from Ipsen, personal fees and non-financial support from Novartis, non-financial support from Imaging Equipment, outside the submitted work. IC reports advisory role for Eli-Lilly, Bristol Meyers Squibb, MSD, Bayer, Roche, Merck-Serono, Five Prime Therapeutics, AstraZeneca, Oncologie International, Pierre Fabre; research funding from EliLilly, Janssen-Cilag, Sanofi Oncology, Merck-Serono; honorarium from Eli-Lilly. AL received travel and educational support from Ipsen, Pfizer, Bayer, AAA, Sirtex Medical, Novartis, Mylan and Delcath Systems; speaker honoraria from Merck, Pfizer, Ipsen and Incyte; advisory honoraria from EISAI and Nutricia; she is a member of the Knowledge Network and NETConnect Initiatives funded by Ipsen. DS reports personal fees from MSD, personal fees and non-financial support from EISAI, personal fees and non-financial support from Ipsen, personal fees from Bayer, non-financial support from Mina Therapeutics, personal fees from Pfizer, personal fees from Novartis, outside the submitted work. TM reports grants from Bayer, grants from BTG, personal fees from BMS, personal fees from EISAI, personal fees from AstraZeneca, personal fees from Tarveda, personal fees from Ipsen, personal fees from MSD, outside the submitted work. DAC reports grants and non-financial support from Servier, during the conduct of the study. HH reports grants and non-financial support from Servier, during the conduct of the study. JWV reports Consulting or Advisory role for Ipsen, Novartis, AstraZeneca, Merck, Delcath Systems, Agios, Pfizer, PCI Biotech, Incyte, Keocyt, QED, Pieris Pharmaceuticals, Genoscience Pharma, Mundipharma EDO; Honoraria from Ipsen; and Speakers’ Bureau for Novartis, Ipsen, NuCana and Imaging Equipment. MGM has received research grant support from Servier, Ipsen and NuCana. She has received travel and accommodation support from Bayer and Ipsen and speaker honoraria from Pfizer, Ipsen and NuCana. She has served on advisory boards for Celgene, Ipsen, Sirtex and Baxalta.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

Trial schema. ECOG, Eastern Co-operative Oncology Group; EP, extrapulmonary; EORTC, European Organisation for Research and Treatment of Cancer; 5-FU, 5-fluorouracil; NEC, neuroendocrine carcinoma; nal-IRI, liposomal irinotecan; PD, poorly differentiated.