To study the efficacy of everolimus combined with temozolomide as first-line treatment in advanced gastroenteropancreatic neuroendocrine carcinoma with a Ki67 of 20-55%, measured as disease control rate (non-progressive disease) at 6 months.

Guidelines for treating advanced gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) advocate the use of combination chemotherapy with a platinum-based chemotherapy combined with etoposide. No other regimen has consistently shown a benefit over this combination. NECs do not respond to treatments usually applied in other neuroendocrine tumours such as somatostatin analogues and interferon. In contrast to metastatic neuroendocrine tumours with a low Ki67, debulking surgery and surgery for liver metastasis is generally not recommended. Cisplatin /carboplatin and etoposide is established as standard treatment of advanced disease based on two small retrospective studies showing a response rate between 41- 67% and median survival of 15-19 months. In the current trial we propose an alternative treatment for a subgroup of patients with GEP-NEC based on new data, with the intention to improve response rates and clinical benefit rate without increasing toxicity

Inclusion criteria

Histologically proven neuroendocrine carcinoma with a Ki67 of 20-55%.Primary gastroenteropancreatic tumor or cancer of unknown primary where metastases are mainly abdominalMeasurable disease according to RECIST by CT/MR

General conditions:

• >18 years;
• WHO/ECOG performance status 0-1.
• Adequate haematological, renal and hepatic functions:
• Written informed consent prior to inclusion

Prior therapy:

• No prior chemotherapy treatment for advanced disease.
• Adjuvant chemotherapy must have ended > 6 months before inclusion.

Prior or current history:

• No curatively resectable disease;
• No other serious illness or medical conditions (including: unstable angina, myocardial infarction within 6 months, unstable diabetes, immune suppression )

Concomitant treatments :

• No concomitant (or within 4 weeks before inclusion) administration of any other experimental drug;
• No other concurrent anti-cancer therapy.

Other :

• Not pregnant or breast feeding. Fertile patients must use adequate contraceptives and fertile females must have a negative pregnancy test.