Everolimus Plus Best Supportive Care vs Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (GI or Lung Origin) (RADIANT-4)

Inclusion Criteria:

• Pathologically confirmed, well differentiated (G1 or G2), advanced (unresectable or metastatic), neuroendocrine tumor of GI or lung origin
• No history of and no active symptoms related to carcinoid syndrome
• In addition to treatment-naive patients, patients previously treated with SSA, Interferon (IFN), one prior line of chemotherapy, and/or PRRT are allowed into the study. Pretreated patients must have progressed on or after the last treatment
• Radiological documented disease progression within 6 months prior to randomization
• Measurable disease
• WHO performance status ≤1
• Adequate bone marrow, liver and renal function

Exclusion Criteria:

1. Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, insulinoma, glucagonoma, gastrinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma
2. Patients with pancreatic NET or NET of origins other than GI or Lung
3. Patients with history of or active symptoms of carcinoid syndrome (e.g. flushing, diarrhea)
4. Patients with more than one line of prior chemotherapy
5. Prior targeted therapy
6. Hepatic locoregional therapy within the last 6 months
7. Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus)
8. Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
9. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
10. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy

11. Patients who have any severe and/or uncontrolled medical conditions such as:

    • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to randomization, serious uncontrolled cardiac arrhythmia
    • active or uncontrolled severe infection
    • liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA)
12. Chronic treatment with corticosteroids or other immunosuppressive agents
13. Known history of HIV seropositivity
14. Pregnant or nursing (lactating) women

Other protocol-defined inclusion/exclusion criteria may apply.