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: 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 = 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 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 clinically 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 QTcF > 470 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.Cardiac failure, clinically significant/symptomatic bradycardia or high-grade AV block
•Concomitant medications known to prolong the QT interval
•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
•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
•Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment
•History or active liver disease such as cirrhosis,decompensated liver disease, chronic active hepatitis or chronic persistent hepatitis
•Quantifiable HBV-DNA or positive hepatitis B surface antigen (HbsAg)
•Quantifiable HCV-RNA
•History of, or current alcohol misuse/abuse within the past 12 months
•Known gallbladder or bile duct disease, acute or chronic pa

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

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