The MetNET-2 Trial

Inclusion Criteria:

* Adult patients (male or female, age \> 18 years)
* Patient with advanced disease, not resectable. The evaluation of unresectable disease will be performed by surgeon of multidisciplinary Milan ENETS Center of Excellence tumour board of Fondazione IRCCS Istituto Nazionale dei Tumori Milano.
* Patients with a histologically documented diagnosis of advanced well differentiated (G1 and G2) GI or lung carcinoids, defined according to the last WHO Classification criteria for NET
* Tumor tissue available for analysis
* Measurable disease and disease progression in the 6 months before study inclusion (according to RECIST vs 1.1), documented and appropriate imaging
* Patient who has received prior treatment with surgery or chemotherapy or somatostatin analogues or m-TOR inhibitors or other systemic antineoplastic/target therapies
* Functioning or non-functioning NETs
* Type-2 Diabetic or normoglycaemic patient
* Documented Octreoscan/PET Ga68 uptake/IHC stain of SSTR2 receptor, within 6 months before study entry
* Basal blood tests:
* Counts of neutrophils in absolute value\> 1.5 x 103 / L
* Platelet count\> 100 x 103 / L
* Hemoglobin\> 9 g/dl
* Total Bilirubin \<1.5 times the upper limit of normal
* AST, ALT \<2.5 times the upper limit of normal
* Alkaline phosphatase \<2.5 times the upper limit of normal
* Values of serum creatinine \<1.5 mg / dl. - CCr ≥ 60 mL / min
* ECOG performance status ≤ 2
* Life expectancy \> 12 months
* Written informed consent
* Female subjects of childbearing potential (not surgically sterile or 2 years postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for at least 60 days after participation in the study. Acceptable methods of contraception include double barrier method \[i.e. condom and occlusive cap (diaphragm or cervical/vault caps)\] spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
* Male subjects with female partners of childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 60 days after participation in the study.

Exclusion Criteria

* Surgery performed within 28 days prior to the beginning of study treatment
* Brain metastasis or spinal cord compression
* Type-1 Diabetes
* Clinically significant cardiovascular disease, such as cardiovascular accidents occurred in less than 6 months, unstable angina, congestive heart failure grade greater than or equal to II (according to the classification of the New York Heart Association NYHA) series cardiac arrhythmias that require treatment
* Uncontrolled high blood pressure, atrial fibrillation
* Cardio-vascular, lung, kidney or hepatic disorders not treated/controlled
* Cirrhosis, acute hepatitis or chronic active hepatitis
* Metabolic disorders, clinical examination or laboratory investigations which contraindicate the use of drugs to study, or patients at high risk of complications from the treatment
* Active or uncontrolled severe infections
* Patients with a condition of metabolic acidosis, acute or chronic, including ketoacitosi
* History of POTUS (alcohol abuse), or habitual intake of alcohol (≥ 3 glasses of alcoholic drinks / day) sufficient to cause hepatotoxicity
* Severe states of dehydration
* Prolonged fasting
* History of immunosuppression, including positive HIV test
* Previous or concomitant oncological pathology, except: basal cell skin cancer, in situ, as long as every other cancer patient disease-free for at least 5 years
* Serious neurological or psychiatric disorders
* Pregnancy or lactation
* Patients that do not use appropriate methods of contraception as specified in the inclusion criteria