Efficacy and Safety of 177Lu-Dotatate PRRT in Metastatic GEP-NEN Patients

Inclusion Criteria:

1. sign written informed consent form

2. age ≥ 18 years

3. pathologically confirmed well-differentiated neuroendocrine tumors;

4. unresectable metastatic tumors confirmed by radiological imaging;

5. Somatostatin receptor positive (SSTR+) disease;

6. Radiological disease progression within 12 months, defined as progressive disease perRECIST 1.1. criteria

7. No more than 2 prior antitumor drugs, including somatostatin analogs, targeted drugsand chemotherapy, with the last dose over 4 weeks;

8. At least 1 measurable lesion (only 1 measurable lymph node lesion is excluded) (routine CT scan >=20mm, spiral CT scan >=10mm, no prior radiation to measurablelesions);

9. Screening laboratory values must meet the following criteria (within past 7 days):hemoglobin ≥ 9.0 g/dL; neutrophils ≥ 1500 cells/ μL; platelets ≥ 100 x 10^3/ μL; totalbilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alaninetransaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis; serumcreatinine ≤1╳ULN;

10. KPS ≥ 70;

11. Predicted survival >=3 months;

12. Negative serum or urine pregnant test within 7 days prior to randomization forchild-bearing age women;

13. Sexually active males or females willing to practice contraception during the studyuntil 30 days after end of study.

Exclusion Criteria:

1. Hypersensitivity to DOTA, lutetium-177, or any excipient of edotreotide or everolimusor any other Rapamycin derivative;

2. Prior antitumor therapy (including corticosteroids and immunotherapy) or participationin other clinical trials within past 4 weeks, or have not recovered from toxicitiessince the last treatment;

3. Received surgery within past 4 weeks, or have not recovered from surgery;

4. Concurrent severe infection；

5. Severe, uncontrolled medical condition that would affect patients' compliance orobscure the interpretation of toxicity determination or adverse events, includingsevere liver disease (active hepatitis, cirrhosis), uncontrolled diabetes orhypertension, or pulmonary disease ( interstitial pneumonia, obstructive pulmonarydisease or symptomatic bronchospasm);

6. Prior long term steroid therapy (excluding short term steroid treatment which iscompleted prior to > 2 weeks of study enrollment)；

7. Meningeal carcinomatosis;

8. Patients with central nervous system(CNS) disorder or peripheral nervous systemdisorder or psychiatric disease；

9. Known history of uncontrolled or symptomatic angina, uncontrolled arrhythmias andhypertension, or congestive heart failure, or cardiac infarction within 6 months priorto study enrollment, or cardiac insufficiency；

10. Pregnant or nursing, or sexually active males or females refuse to practicecontraception during the study until 30 days after end of study;

11. History of other malignancy. However, subjects who have been disease-free for 5 years,or subjects with a history of completely resected non-melanoma skin cancer orsuccessfully treated in situ carcinoma, are eligible；

12. Person with no capacity (legally) or inappropriate to continue study treatment forethics/medical reasons；

13. Underlying medical condition that, in the Investigator's opinion, would increase therisks of study drug administration or obscure the interpretation of toxicitydetermination or adverse events.