Due to difficulty in early diagnosis, patients often present with gastro-enteropancreatic neuroendocrine (GEP-NET) tumours in advanced stages. Lanreotide autogel (LAN) 120mg/4 weeks has been shown to improve progression-free survival (PFS) vs. placebo in advanced, non-functioning GEP-NETs and is licensed for this indication. However, treatment options beyond LAN are limited for patients with midgut or pancreatic NETs. Temozolomide is an alkylating agent that has shown efficacy against NETs in combination with other drugs. The aim of SONNET (lanreotide [Somatuline®] in NET with temozolomide) is to evaluate the efficacy (response profile) and safety of LAN 120 mg combined with temozolomide in patients with progressive GEP-NETs.
This is a phase 2, open-label, prospective, multicentre, non-comparative pilot study. To reach the statistical analysis target of 40 evaluable patients, treatment is planned for 48 patients (≥18 years) with a locally advanced, or metastatic, G1/G2, functioning or non-functioning GEP-NET, or a NET of unknown primary that is progressive according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. SONNET consists of a screening phase (4 weeks), a combination phase (6 months), and a maintenance phase (6 months). During the combination phase, patients receive LAN 120 mg/4 weeks plus temozolomide at 150 mg/m2/day for 5 days in month 1, increasing to 200 mg/m2/day in months 2–6. At the end of the combination phase, patients showing a clinical benefit as assessed by the primary endpoint (disease control rate [complete response + partial response + stable disease], assessed centrally using RECIST v1.1) receive LAN 120 mg/4 weeks (for functioning NETs), or are randomized to receive LAN 120 mg/4 weeks or no treatment (for non-functioning NETs) for the duration of the maintenance phase. Secondary endpoints include disease control rates at the end of the maintenance phase; time to progression or death (PFS) within 12 months of initiating combination treatment; time to response within the 12-month study period and safety. Recruitment will be finalized in summer 2016.
Clinical trial identification
Protocol number = A-94-52030-268 EudraCT number = 2013-001697-17 Clinical Trials.gov = NCT02231762
Legal entity responsible for the study
IPSEN Pharma GmbH, Germany
D. Hörsch: Personal fees/other from: Lexicon Pharmaceuticals, Inc. Grants/personal fees/other from: Novartis Pharma. Personal fees/other from: Ipsen Pharma. Personal fees/other from: Pfizer Pharma, outside the submitted work.
M. Raderer: Advisory boards: Ipsen, Novartis, Celgene, Mundipharma, Jannsen Cilag, Roche. Honoraria/Speaker: Ipsen, Novartis, Celgene, Swedish Orphan.
H. Lahner: Advisory board: Pfizer, Novartis. Consultancy fees: Pfizer, Novartis, Ipsen. Research support: Novartis. Speaker/lecturer: Pfizer, Novartis, Ipsen.
A. Rinke: Advisory board meetings of Ipsen, Novartis and Pfizer.
T. Denecke: Payment by Ipsen for central read of study patients.
A. Raspel, P. Hoffmanns: Ipsen employee.
M. Pavel: Advisory board: Ipsen, Novartis, Lexicon. Consultancy fees: Ipsen, Novartis, Lexicon. Research support: Novartis, Ipsen.
All other authors have declared no conflicts of interest.