Pancreatic neuroendocrine tumors (also called pancreatic endocrine tumors or islet cell tumors (ICT)) MedDRA version: 9.1 Level: LLT Classification code 10033630 Term: Pancreatic islet cell neoplasm malignant NOS
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have advanced (unresectable or metastatic) biopsy-proven pancreatic NET 2. Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma 3. Patients must have radiological documentation of progression of disease within 12 months prior to randomization. If patient received anti-tumor therapy during the past 12 months, he/she must have radiological documentation of progression of disease while on or after receiving the therapy 4. Measurable disease per RECIST criteria using Triphasic Computed Tomography (CT) scan or multiphase MRI for radiologic assessment 5. Adequate bone marrow function as shown by: ANC = 1.5 x 109/L, Platelets = 100 x 109/L, Hemoglobin >9 g/dL 6. Adequate liver function as shown by: • Serum bilirubin = 1.5 x ULN • INR =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma are not eligible 2. Cytotoxic chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to randomization 3. Hepatic artery embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation/ radiofrequency ablation of hepatic metastasis within 2 months of enrollment 4. Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus). 5. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 x ULN 6. 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 • cirrhosis, chronic active hepatitis or chronic persistent hepatitis • severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air). • active, bleeding diathesis 7. Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent 8. Patients with a known history of HIV seropositivity 9. No other prior or concurrent malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for = 3 years. 10. Female patients who are pregnant or nursing (lactating), or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether treatment with RAD001 10 mg/d plus best supportive care prolongs the progression free survival (PFS) compared to treatment with Placebo plus best supportive care in patients with advanced pancreatic neuroendocrine tumor.;Primary end point(s): Progression free survival (PFS);Secondary Objective: • To evaluate the effect of RAD001 on other tumor endpoints: objective response rate (CR or PR), response duration • To compare overall survival (OS) between the study arms • To determine the safety and tolerability of RAD001 (10 mg/d) in patients with advanced Pancreatic Neuroendocrine Tumor • To characterize the pharmacokinetics of RAD001 in Pancreatic NET indications • To compare changes from baseline in chromogranin A (CgA) and follow other biochemical tumor markers produced by the tumor that are elevated at baseline, during subsequent visits • To characterize pre-treatment tumor samples by immunohistochemical and genetic analyses indicating activation of the mTOR pathway. • To assess the relationship between RAD001 steady state levels, tumor response, and chromogranin A response (50% decrease from baseline) • To determine the effects of RAD001 on plasma antigenic molecules e.g. VEGF, basic FGF, PLGF, sVEGFR1, and sVEGFR2 | — |
Countries
Belgium, France, Germany, Greece, Italy, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed