A study of everolimus plus best supportive care versus placebo plus best supportive care in the treatment of patients with advanced neuroendocrine cancer of gastrointestinal or lung origi
- Conditions
- Advanced neuroendocrine tumor (NET) of GI or lung originMedDRA version: 14.1Level: PTClassification code 10052399Term: Neuroendocrine tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-002887-26-HU
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 285
1.Pathologically confirmed, well differentiated (G1 or G2), advanced (unresectable or metastatic), neuroendocrine tumor of GI or lung origin.
2.No history of and no active symptoms related to carcinoid syndrome (or other hypersecretory syndromes).
3.Patients treated with prior SSA and/or Interferon (IFN) may be included. These patients must discontinue treatment prior to the day of randomization as follows:
4.Radiological documented disease progression within 6 months prior to randomization
5.Measurable disease
6.WHO performance status =1
7.Adequate bone marrow, lifer and renal function
Other protocol-defined inclusion/exclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 95
1.Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, gastrinoma, goblet cell carcinoid, 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.Prior systemic cytotoxic chemotherapy or targeted therapy.
6.Hepatic intra-arterial embolization within the last 6 months (or 1 month if there is measurable disease in other organs besides the liver)
7.Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus).
8.Known intolerance or hypersensitivity to everolimus or other rapamycins (e.g. sirolimus, temsirolimus).
9.Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus.
10.Uncontrolled diabetes mellitus.
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, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
Other protocol-defined exclusion criteria may apply.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Determinate whether treatment with everolimus plus best supportive care prolongs PFS compared to placebo plus best supportive care in patients with advanced NET of GI or lung origin;Secondary Objective: Safety evaluation and tolerability of everolimus<br>;Primary end point(s): Tumor assesments as per modified RECIST 1.0 based on local assessment. Progression free survival (PFS);Timepoint(s) of evaluation of this end point: Every 12 weeks until disease progression, start of futher anti-tumor therapy or intolerable toxicity, whichever comes first.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Overall Survival (OS).<br>2. Safety evaluation and efficacy in everolimus.<br>3. FACT-G total score over time.<br>4. Objective response rate (ORR).<br>5. Changes from baseline in Chromogranin A (CgA) and Neuron specific enolase (NSE) levels.<br>6. Pre-dose concentration (Cmin);Timepoint(s) of evaluation of this end point: 1. Continuously during the treatment period. Every 12 weeks during follow-up. <br>2. Continuously<br>3. Every 12 weeks until start of futher anti-tumor therapy.<br>4. Every 12 weeks until disease progression, start of futher anti-tumor. therapy or intolerable toxicity, whichever comes first.<br>5. Every visit until end of treatment.<br>6. Cycle 2 (Day 29)