A clinical research study to find out if everolimus alone or everolimus in combination with pasireotide LAR (LAR stands for long-acting release) is safe and has beneficial effects in people who have advanced pancreatic neuroendocrine tumor (PNET).

• Conditions: advanced progressive pancreatic neuroendocrine tumors (PNET); MedDRA version: 14.1Level: HLTClassification code 10014712Term: Endocrine neoplasms malignant and unspecified NECSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-023183-40-IT
• Lead Sponsor: OVARTIS FARMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-20
• Last Update Posted: 19 October 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Advanced (unresectable or metastatic), histologically confirmed well differentiated (low to intermediate grade) pancreatic neuroendocrine tumor (PNET). 2. Radiological documentation of progressive disease within the last 12 months prior to randomization. 3. Measurable disease per RECIST Version 1.0 determined by multiphase MRI or triphasic CT. 4. Adult patients (male or female) = 18 years of age. 5. WHO performance status = 2 6. Adequate bone marrow function: • WBC = 2.5 x 109/L, • ANC = 1.5 x 109/L, • Platelets = 100 x 109/L, • Hb = 9 g/dL 7. No evidence of significant liver/pancreas disease:• Serum bilirubin = 1.5 x ULN,• INR < 1.3, • ALT and AST = 3 x ULN,• Serum lipase and amylase = 2 x ULN 8. Serum creatinine = 2.0 mg/dl and estimated glomerular filtration rate (eGFR) > 30 ml/min/m2 (calculated with MDRD formula). 9. Written informed consent is to be obtained prior to any screening procedures.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

1. Patients currently requiring SSA treatment. 2. Patients who received prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus), or pasireotide. 3. Patients who received any cytotoxic chemotherapy, targeted therapy, SSAs, or biotherapy within the last 4 weeks. 4. Patients with more than 2 prior systemic treatment regimens 5. Patients with a known hypersensitivity to SSAs. 6. Patients with a known hypersensitivity to any component of the pasireotide LAR or s.c. formulations, everolimus or other rapamycin analogs (sirolimus, temsirolimus) or to their excipients. 7. Prior treatment with radiolabeled SSAs within the last 12 months. 8. Patients with hepatic artery embolization, cryoablation or radiofrequency ablation of hepatic metastasis within the last 3 months prior to randomization. 9. Patients who have received radiotherapy of target lesions. Patients who have received local radiotherapy of non-target lesions for local symptom control within the last 4 weeks must have recovered from any adverse effects of radiotherapy prior to randomization. 10. Patients who have undergone major surgery/surgical therapy for any cause within 1 month or surgical therapy of loco-regional metastases within the last 3 months prior to randomization. Patients should have recovered from the treatment and have a good clinical condition before entering this study. 11. Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent. 12. Patients with symptomatic cholelithiasis. 13. Patients who are not biochemically euthyroid. Patients with history hypothyroidism are eligible if they are on adequate and stable replacement thyroid hormone therapy for at least 3 months. 14. Patients with abnormal coagulation (PT [INR] or aPTT elevated by 30% above normal limits). 15. QT-related exclusion criteria: • Patients with a baseline QTcF > 450 ms, • History of syncope or family history of idiopathic sudden death, Long QT syndrome, • Sustained or clinically significant cardiac arrhythmias, • Patients with risk factors for torsades de pointes: Potassium < 3.0 mmol/L, magnesium < 0.4 mmol/L or, calcium < 1.75 mmol/L at baseline. If the electrolyte abnormalities are corrected prior to start of study drug, the patient may become eligible for the trial. Cardiac failure, clinically significant/symptomatic bradycardia or high-grade AV block, • Concomitant medications known to prolong the QT interval (see Appendix 2). • Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes mellitus or Parkinson’s disease), HIV, liver cirrhosis, uncontrolled hypothyroidism or cardiac failure. 16. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: • Uncontrolled diabetes as defined by HbA1c = 8% despite adequate therapy, • Fasting serum cholesterol > 300 mg/dL (7.75 mmol/L) OR fasting triglycerides > 2.5 x ULN despite appropriate lipid lowering medication. • Severely impaired lung function defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air. DLCO should be adjusted to hemoglobin value and patient lung volumes. • Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunodeficiency, including a positive HIV test result (ELISA and Western blot). A HI

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified