Sequentiality of Everolimus and STZ-5FU in Advanced Pancreatic Neuroendocrine Tumor

Inclusion Criteria:

* Histologically proven diagnosis of unresectable or metastatic, advanced pancreatic NET.
* Documented confirmation of pancreatic NET G1 or G2 as per European Neuroendocrine Society (ENETS) classification system.
* Patients from whom a paraffin-embedded primary tumour or metastasis block is available and to be sent by Courier.
* Before study inclusion, patients must show progressive disease documented by radiology 12 months prior to study inclusion. Treatment naive patients can be also included if the patient needs active treatment with either chemotherapy or everolimus.
* Presence of measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.0, documented by a Triphasic Computed Tomography (CT) scan or multiphase MRI radiological assessment.
* Previous treatment with somatostatin (SS) analogues is allowed. Only those patients with active functioning syndrome at entry can continue with SS analogues during the study.
* Adequate bone marrow and renal functions, and serum fasting cholesterol
* Women with child-bearing potential must have a negative serum pregnancy test.
* Written Informed Consent obtained according to local regulations

Exclusion Criteria:

* Previous treatment with chemotherapy and/or mTOR inhibitors or tyrosine kinase inhibitors.
* Immune therapy or radiation therapy within 4 weeks prior to the patient entering the study.
* Hepatic artery embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation/radiofrequency ablation of hepatic metastasis within 2 months of enrolment.
* Previous treatment with Peptide-Receptor Radionuclide Therapy (PRRT) within the last 6 months and/or without progression following PRRT.
* Uncontrolled diabetes mellitus.
* Any severe and/or uncontrolled medical conditions.
* Treatment with potent inhibitors or inducers of Cytochrome P450 3A4 (CYP3A) isoenzyme within 5 days immediately before the start of treatment.
* Patients on chronic treatment with corticosteroids or any other immunosuppressive agent.
* Patients known to be HIV seropositive.
* Known intolerance or hypersensitivity to everolimus or its excipients or other rapamycin analogues. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
* Known intolerance or hypersensitivity to 5FU or STZ or its excipients (notice that this criterion includes patients with known deficit of dihydropyrimidine dehydrogenase deficiency -DPD).
* Pregnant, lactating women or fertile adults not using effective birth control methods.
* For administrative matters (insurance) patients ≥ 95 are not allowed during the trial.

Only those patients coming from the hospital pool will be included in SEQTOR trial (e.g. persons detained in an institution as a result of an official or court order are excluded).