Efficacy and Safety of Radiotherapy Compared to Everolimus in Somatostatin Receptor Positive Neuroendocrine Tumors of the Lung and Thymus.

Inclusion Criteria:

1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved writteninformed consent.

2. Patients ≥ 18 years of age.

3. Patients who have histologically confirmed metastatic or locally advancedunresectable well/moderately differentiated; World Health Organization (WHO]) 2015criteria; neuroendocrine tumor of lung (typical and atypical carcinoids) or thymusorigin either functioning or non-functioning.

4. Patients must have the appropriate pathological features based on WHOclassification, and description of proliferation activity as indicated by mitoticcount per 10 high-power fields (HPF) and presence of necrosis, or Ki67 index.

5. In SSTR imaging all RECIST v1.1 selected target lesions and all other lesionsconsidered dominant by the investigator should be positive. If an fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET) is performed (not mandatory), allFDG-PET positive RECIST v1.1 target lesions and all other FDG-PET positive lesionsconsidered dominant by the investigator should also be positive in SSRT imaging.

6. Lesions must have shown radiological evidence of disease progression in the 12months prior to inclusion in the study. Patients who were receiving systemicanticancer therapy, progression should be documented on therapy or after stoppingtherapy due to adverse events or other reasons. Patients without prior therapy,documentation of progression is also mandatory to watch and wait strategy or duringthe follow up after surgery.

7. Patients may be included in first-line therapy (systemic treatment naïve) or mayhave experienced progression on somatostatin analogues or additional systemictreatments, which may include but not limited to chemotherapy, targeted agents orimmunotherapy (maximum of 2 prior systemic anti-tumor treatments). Note: Somatostatin analogues for patients with functioning tumors are allowed.

8. Patients have radiographically documented and measurable metastatic or locallyadvanced disease at baseline according to RECIST v1.1.

9. An archival tumor tissue sample should be available for submission to the centrallaboratory prior to study treatment (36 months). If an archival tumor tissue sampleis not available, a new biopsy tissue sample should be provided if feasible.

10. Patients who have Eastern Cooperative Oncology Group (ECOG) performance status of 0or 1.

11. Adequate organ and bone marrow function based upon meeting all of the followinglaboratory criteria:

12. Neutrophil count (ANC) ≥ 1,500/mm^3

13. Platelet count ≥ 75 × 10^9/L

14. Hemoglobin ≥ 8 g/dL

15. Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjectswith Gilbert's disease or liver metastases

16. Creatinine clearance (CrCl) ≥ 40 mL/min as estimated by the Cockcroft-Gaultformula or as measured by 24-hour urine collection (GFR can also be usedinstead of CrCl). Note: renal tract obstruction is not allowed.

17. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULNor ≤ 5 x ULN for subjects with liver metastases

18. Female subject must provide a negative urine pregnancy test at screening, and mustagree to use a medically accepted and highly effective birth control method (i.e.those with a failure rate less than 1%) for the duration of the study treatment andfor 6 months after the final dose of study treatment.

19. Female patients must agree not to breastfeed or donate ovules starting at screeningand throughout the study period, and for at least 6 months after the final studydrug administration.

20. Male patients must agree not to donate sperm starting at screening and throughoutthe study period, and for at least 6 months after the final study drugadministration.

21. Male patients with a pregnant or breastfeeding partner(s) must agree to abstinenceor use a condom for the duration of the pregnancy or time the partner isbreastfeeding throughout the study period and for at least 6 months after the finalstudy drug administration.

22. Subject agrees not to participate in another interventional study while on treatmentin the present study.

Exclusion Criteria:

1. Patients who are not able to swallow tablets.

2. Patients with poorly-differentiated or high-grade neuroendocrine carcinoma (i.e.large cell neuroendocrine carcinoma of lung, small cell lung cancer) or mixed tumors (i.e. adenocarcinoid tumor) are not eligible.

3. Patients with brain mets unless stable on treatment for > 12 weeks and with noevidence of raised intracranial pressure or mass effect.

4. Patients who have ongoing clinically significant toxicity (Grade 2 or higher withthe exception of alopecia) associated with prior treatment (including systemictherapy, radiotherapy or surgery).

5. Patients who have a recent diagnosis of another malignancy (within 12 months priorto inclusion), patients who are on active treatment for other cancer before thefirst dose of study drug, or any evidence of residual disease from a previouslydiagnosed malignancy.

6. Patients who have a known active Hepatitis B (e.g., HBsAg reactive) or activehepatitis C (e.g., hepatitis C virus (HCV) RNA [qualitative] is detected). Patientswho have a known history of human immunodeficiency virus (HIV) infection (HIV 1 or 2).

7. Patients who have received a live vaccine up to 4 weeks prior to the first dose oftrial treatment. Note:Live attenuated vaccines should not be administered during the trial treatmentand over the next 3 months after the last treatment dose.

8. Patients who have documented history of a cerebral vascular event (stroke ortransient ischemic attack), unstable angina, myocardial infarction, or cardiacsymptoms (including congestive heart failure) consistent with New York HeartAssociation Class III-IV within 6 months prior to the first dose of study drug.

9. Prior peptide receptor radionuclide therapy (PRRT) or mammalian target of rapamycin (mTOR) inhibitors (e.g. deforolimus, everolimus, sirolimus, temsirolimus, etc.); orhepatic radio-embolization (within 6 months prior to first dose of study treatment).

10. Prior radiotherapy or major surgery within 12 weeks prior to the first dose of studydrug.

11. Patients who have had chemotherapy, biologics, investigational agents, and/orantitumor treatment with immunotherapy that is not completed 4 weeks prior to thefirst dose of study drug.

12. Patients who have known hypersensitivity to Everolimus or to any excipient containedin the drug formulation of Everolimus.

13. Patients who have known hypersensitivity to 177Lu-edotreotide or to any excipientcontained in the drug formulation of 177Lu-edotreotide or the nephroprotective aminoacid solution (AAS).

14. Current spontaneous urinary incontinence preventing safe administration of theinvestigational medicinal product (IMP), in the investigator's opinion.

15. Patients who have other underlying medical conditions that, in the opinion of theinvestigator, would impair the ability of the subject to receive or tolerate theplanned treatment and follow-up.