1165TiP - NETTER-1: First pivotal Phase III study evaluating 177Lu-DOTATATE in midgut neuroendocrine tumours

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Neuroendocrine Cancers
Surgery and/or Radiotherapy of Cancer
Presenter Maribel Lopera Sierra
Citation Annals of Oncology (2014) 25 (suppl_4): iv394-iv405. 10.1093/annonc/mdu345
Authors M. Lopera Sierra1, D. Kwekkeboom2, M.F. Mariani3, L. Bodei4, P. Santoro3, E.P. Krenning2
  • 1Medical Affaires, Advanced Accelerator Applications, 01630 - Saint Genis Pouilly/FR
  • 2Nuclear Medicine, Erasmus University Medical Center, 3015 CE - Rotterdam/NL
  • 3Research And Development, Advanced Accelerator Applications, 01630 - Saint Genis Pouilly/FR
  • 4Nurclear Medicine Division, European Institute of Oncology, Milan/IT

Abstract

Background

Currently, there is an unmet medical need for long-term effective treatment of inoperable, gastro-entero-pancreatic neuroendocrine tumours (GEPNETs). Patients having midgut neuroendocrine tumours (30-50% of all NETs) have very limited therapeutic options: the only registered products (i.e. somatostatin analogues, such as Octreotide®) are approved for symptomatic treatment, and all other potential treatments are either investigational, or off-label. Tumor-targeted peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA0-Tyr3-Octreotate (177Lu-DOTATATE) has been in use since 2000, with over several thousands of patients already treated worldwide. The results are very encouraging in terms of tumor response, safety and quality of life improvement.

Trial design

This is the first Phase III multicentric, stratified, open, randomized, controlled, parallel-group study, comparing 177Lu-DOTATATE with Octreotide LAR (Sandostatin® LAR Depot) in patients with inoperable, progressive, somatostatin receptor positive midgut carcinoid tumours. Treatment with a cumulative dose of 29.6 GBq of 177Lu-DOTATATE (7.4 GBq x 4 at 8 ± 1-week intervals) plus supportive care with 30 mg Octreotide LAR will be compared to 60 mg Octreotide LAR (injections at 4-week intervals). The primary objective is Progression Free Survival (PFS) between the two arms. Objective tumour assessment is performed every 12 weeks until PFS. Tumor progression is assessed with an independent image reading center. The main secondary objectives are to compare Objective Response Rate, Overall Survival (OS), and Time to Tumour Progression between the two arms, and to assess safety, tolerability and health-related quality of life. Dosimetry, pharmacokinetics and ECG evaluations in patients treated with 177Lu-DOTATATE will also be performed. The study will randomize 230 patients (1:1 to each arm). The OS period includes 18-month accrual plus 5 years follow-up. There are 35 European and 15 USA sites involved. Recruitment is ongoing, and the first patient was enrolled in July 2012. An independent Data Safety Monitoring Board (DSMB) is supervising the conduct of the study and regularly assesses the safety outcome.

Disclosure

M. Lopera Sierra and M.F. Mariani: The author is an employee and shareholder of Advanced Accelerator Applications; D. Kwekkeboom and E.P. Krenning: The author is a shareholder of Advanced Accelerator Applications; P. Santoro: The author is an employee of Advanced Accelerator Applications. All other authors have declared no conflicts of interest.