A randomized, open-label phase II multicenter study evaluating the efficacy of oral Everolimus alone or in combination with Pasireotide LAR i.m. in advanced progressive pancreatic neuroendocrine tumors (PNET)

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 160

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 < 1.3,
• ALT or 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:
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

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 < 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 O

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials