Pancreatic well differentiated neuroendocrine tumors (NET) MedDRA version: 20.0 Level: LLT Classification code 10067518 Term: Pancreatic neuroendocrine tumor System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Bevacizumab
Product Name: Bevacizumab
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Concentration unit: mg
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Well differentiated pancreatic neuroendocrine tumor grade 1 (NET G1) or grade 2 (NET G2): mitotic index 50%, symptoms related to the tumour or its metastases, Ki67>10%) 3. Patient with at least one measurable target tumor by RECIST 1.1 that thas never been irradiated 4. Patient with a life expectancy greater than 3 months 5. Men or women with performance status (ECOG) = 2 6. Age = 18 years 7. Adequate hematological function: neutrophil count (ANC) = 2x109/L, platelets ? 75x109/L, hemoglobin ? 10g/dl (blood transfusions are accepted to reach this level). 8. Adequate liver function: serum bilirubin ?3 x upper limit of normal (ULN); aminotransferases and alkaline phosphatase levels ? 2.5 ULN (? 5 ULN if liver metastases), TP > 50% 9. Proteinuria = 1g/24 h, blood creatinine less than 120 µmol/L and creatinin clearance = 60 ml/min as calculated by Cockroft-Gault formula 10. Absence of active bleeding, coagulopathy or pathologic condition that would confer a high risk of bleeding 11. Prior treatment with somatostatin analogues, everolimus or sunitinib is allowed 12. Negative serum pregnancy test = 72 hours before randomization (for women of childbearing potential only). Sexually active women of childbearing potential must agree to use a highly effective method of contraception or to abstain from sexual activity during the study and for at least 6 months after the last study treatment administration. Sexually active males patients must agree to use condom during the study and for at least 6 months after the last study treatment administration. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception. 13. Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol. 14. Patient affiliated to a social security regimen or beneficiary of such regimen 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 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Disease accessible to resection or percutaneous method of destruction 2. Any known allergy or contraindication to the treatments used in the trial, and in particular known DPD deficiency. 3. Patient previously treated with chemotherapy for the neuroendocrine tumour 4. Patient have received any other antitumor therapy: chemotherapy, immunotherapy 5. Other serious diseases such as respiratory failure or congestive heart failure, angina pectoris not medically controlled. History of myocardial infarction, within 6 months prior to study entry, uncontrolled hypertension and arrhythmias, concomitant severe infection or uncontrolled diabetes mellitus. 6. Subjects with a history of chronic or acute hepatitis C or B infection. 7. Surgery during the 5 weeks preceding the randomization 8. History of cancer (except basal cell skin or carcinoma in situ carcinoma of the cervix) within 5 years prior to entry into the trial. But patients with cancers that have been treated more than 5 years ago and are considered as cured are eligible. 9. Neurological or psychiatric pathology that may interfere with adherence to treatment 10. Patients have received yellow fever vaccine within 30 days prior to the first dose of trial treatment. 11. Patient with pernicious anaemia and other megaloblastic anaemias secondary to the lack of Vitamin B12 12. Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies 13. Hypersensitivity to study drugs or any of its excipients 14. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent 15. Pregnant or breast feeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare the effect of capecitabine (cape) + temozolomide (temo) and of 5FU + streptozotocin (strepto) given with a new schedule (LV5FU2 + strepto), two of the most used chemotherapy regimens in the treatment of well differentiated pancreatic neuroendocrine tumors alone or in combination with bevacizumab (beva) on progression-free survival (PFS) and compare the chemotherapy regimens alone or with beva (two by two design) on the same criteria.;Secondary Objective: Compare the tolerance (NCI-CTCAE) and other parameters of efficacy of two different schedules of chemotherapy, and the effect on tolerance and efficacy of the addition of beva to chemotherapy: Other parameters of efficacy will include: objective response (OR) and its duration, quality of life (EORTC QLQC 30), and overall survival (OS). ;Primary end point(s): Progression-free survival (PFS) rate defined as the delay from the date of randomization to the date of progression whatever the treatment received at the time of occurence, the date of death whatever its cause in the absence of progression, or date of last follow-up if the patient is alive without progression. ;Timepoint(s) of evaluation of this end point: 6 months after the last study drug administration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The other objectives of the trial are to evaluate objective response rate (ORR) and its duration, quality of life (EORTC QLQC 30), overall survival (OS) and toxicity (NCI-CTCAE v4);Timepoint(s) of evaluation of this end point: 6 months after the last study drug administration | — |
Countries
France
Contacts
Public ContactCRA
Gustave Roussy
Outcome results
None listed