Everolimus Plus Best Supportive Care vs Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (GI or Lung Origin)
Condition: Advanced NET of GI Origin; Advanced NET of Lung Origin; Neuroendocrine Tumors
MeSH terms: Neuroendocrine Tumors
Intervention: Everolimus; Placebo; Best suportive care (BSC)
Intervention description: Participants were treated with everolimus 10 mg (two 5 mg tablets) once daily orally taken; Participants were treated with two tablets of matching placebo once daily orally taken.; Best supportive care includes all care provided to participants deemed necessary by the treating physician, such as but not restricted to anti-diarrheals and analgesics. The optimal care of the patient is based on the treating physician's best medical judgment.
Intervention MeSH terms: Everolimus
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 302.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neuroendocrine tumor; NET; progressive; advanced; gastrointestinal; GI or lung origin; nonfunctional; everolimus; Advanced NET of GI origin; Advanced NET of lung origin

Summary:

      The purpose of this study is to compare the antitumor activity of everolimus plus best
      supportive care versus placebo plus best supportive care in patients with progressive
      nonfunctional neuroendocrine tumor (NET) of gastrointestinal (GI) or lung origin without a
      history of, or current symptoms of carcinoid syndrome.
    

Eligibility criteria:

        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 were allowed into the
             study. Pretreated patients had to 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:

          -  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

          -  Patients with pancreatic NET or NET of origins other than GI or Lung

          -  Patients with history of or active symptoms of carcinoid syndrome (e.g. flushing,
             diarrhea)

          -  Patients with more than one line of prior chemotherapy

          -  Prior targeted therapy

          -  Hepatic intra-arterial embolization within the last 6 months. Cryoablation or
             radiofrequency ablation of hepatic metastases within 2 months of randomization

          -  Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus)

          -  Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g.
             sirolimus, temsirolimus)

          -  Known impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of oral everolimus

          -  Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy

          -  Patients who had 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)

          -  Chronic treatment with corticosteroids or other immunosuppressive agents

          -  Known history of HIV seropositivity

          -  Pregnant or nursing (lactating) women

        Other protocol-defined inclusion/exclusion criteria might apply.