advanced progressive pancreatic neuroendocrine tumors (PNET) MedDRA version: 14.1 Level: PT Classification code 10067517 Term: Pancreatic neuroendocrine tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: pasireotide
Product Code: SOM230
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: Pasireotide
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
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 total bilirubin = 1.5 x ULN, • INR 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: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients currently requiring SSA treatment. 2. Patients who received prior therapy with mTOR inhibitors 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. 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 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 O
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the treatment effect of everolimus in combination with pasireotide LAR relative to everolimus alone on progression-free survival (PFS) in patients with advanced PNET and to assess the predictive probability of success in a possible subsequent phase III study once 80 PFS events have been observed.; Secondary Objective: To evaluate the safety and tolerability profile of everolimus alone or in combination with pasireotide LAR • To evaluate the Objective Response Rate (ORR) and Disease Control Rate (DCR) • To evaluate the duration of response (DoR) • To evaluate overall survival (OS) • To estimate the treatment effect on PFS and to assess the predictive probability of success in a possible subsequent phase III study once 105 PFS events have been observed • To assess pharmacokinetic (PK) exposures of everolimus and pasireotide LAR • To assess potential PK drug-drug interactions between everolimus and pasireotide LAR ;Primary end point(s): PFS per RECIST 1.0. PFS is defined as the time from randomization to the date of the first documented tumor progression or death from any cause, whichever comes first | — |
Countries
Australia, Belgium, Brazil, Denmark, Germany, Hungary, Italy, Japan, Netherlands, Spain, Sweden, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactMedical Collaboration Centre
Novartis Pharmaceuticals UK Ltd
Outcome results
None listed