Treatment of Neuroendocrine Tumors (NETs) With Combination of Everolimus and Radiolabeled Somatostatin Analogue

Inclusion Criteria:

* Age \> 18 years old.
* Histologically confirmed well to moderately differentiated neuroendocrine tumors of GI, lung or pancreatic origin. The grading follows the WHO grading system (Appendix III).
* Measurable disease by CT or MRI.
* Positive Tc-99m Octreotide scan or Ga-68 Octreotate scan (Positive means uptake at tumor sites).
* Advanced disease which are not treatable by surgical resection.
* Documented progressive disease within the past 12 months.
* WHO Performance Status 0 - 2.
* Fasting blood sugar ≤ 1.5 Χ Upper Limit of Normal (ULN).
* Fasting triglycerides ≤ 2.5 Χ Upper Limit of Normal (ULN), and fasting cholesterol ≤ 300 mg/dl or ≤ 7.75 ml/l.
* Adequate renal function with creatinine clearance ≥ 60 ml/l.
* Adequate hepatic function:
* Total bilirubin ≤ 1.5 Χ Upper Limit of Normal (ULN)
* Liver Function Tests (Serum aspartate aminotransferase and alanine transaminase levels) ≤ 2.5 Χ ULN (and ≤ 5 Χ ULN, in case of presence of liver metastasis)
* Adequate hematological values:
* Absolute neutrophil count ≥ 1 x 109/L
* Platelet count ≥ 100 x 109/L
* Signed written informed consent before enrolment.

Exclusion Criteria:

* Readily completely Resectable disease.
* Prior therapy with everolimus or systemic chemotherapy.
* Prior chemoembolization, radio-embolization, or bland embolization within 6 months before enrolment. Likewise, patients are ineligible if had undergone conventional radiotherapy, radiofrequency ablation, cryoablation or alcohol injection within 1 month prior to enrolment.
* Prior long acting somatostatin analogue within 1 month prior to enrolment. Short acting somatostatin analogue is allowed as long as it is not administered within 12 hours before or /and 12 hours after the administration of the intravenous radiolabelled Lu-177 DOTATATE Therapy.
* Presence of Central Nervous System metastasis.
* Previous malignancy within 5 years, except adequately treated non melanomatous skin cancer or in situ cervical cancer
* Other active malignancy.
* HIV infection.
* Severe or uncontrolled medical conditions, such as:
* Active uncontrolled severe infection
* History of invasive fungal infection.
* Child C liver dysfunction.
* Severely impaired lung function.
* Psychiatric or mental disorder, precluding understanding of the information of the trial related topics and giving valid informed consent.
* Any psychological, familial, geographic or social circumstances which could impair the patient's ability to participate in the trial and comply with follow up.
* Treatment with other anti-cancer therapy.
* Known hypersensitivity to any of the study drugs.
* Pregnant or breast feeding women.