Assessment of the efficacy of bevacizumab in combination with Folfiri as second-line treatment after the failure of the cisplatin (or carboplatin)-etoposide combination in patients suffering from an advanced inoperable poorly differentiated neuroendocrine carcinoma of an unknown or gastroentero-pancreatic primary cancer. A phase 2 non-comparative randomized study. PRODIGE 41 - BEVANEC study
- Conditions
- euroendocrine carcinomaMedDRA version: 20.0Level: PTClassification code 10057270Term: Neuroendocrine carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001305-16-FR
- Lead Sponsor
- Hospices Civils de Lyon - Direction de la Recherche Clinique et de l'Innovation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
- Man or woman aged = 18 years old,
- Poorly differentiated neuroendocrine carcinoma (NEC) from a gastroentero-pancreatic (GEP) primary or an unknown primary cancer, locally advanced and/or metastatic (according to the WHO 2010),
- Centralized review of the diagnostic by a consulting pathologist specializing in NET (TENPATH network),
- Recommendation of a second-line chemotherapy after progression documented using the RECIST criteria v.1.1 and after a first-line chemotherapy treatment by cisplatin (or carboplatin) + etoposide or in the case of progression in the 6 months following the discontinuation of this first-line treatment,
- Patients presenting at least one measurable target lesion according to the RECIST criteria v.1.1, in an area not previously irradiated,
- General condition inferior or equal 2 (WHO),
- Patient who signed the informed consent form.
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 64
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
1) Relating to the tumor, the patient and the previous treatment:
- Well differentiated gastroentero-pancreatic neuroendocrine tumor (NET G1 and G2 according to the WHO 2010),
- Mixed tumor,
- First-line chemotherapy other than cisplatin (carboplatin) and etoposide,
- All malignant disease in the three year before randomization, with the exception of basal cell carcinoma or in situ cervical cancer treated for curative purposes,
- A pregnant or breastfeeding woman,
- Lack of efficient contraception (for men or women of reproductive age),
- All medical, geographical, social, and psychological conditions or a legal situation that will not allow the patient to finish the study or sign an informed consent form.
2) Relating to the chemotherapy (Folfiri):
- Any of the following uncontrolled progressive diseases in the 6 months before randomization: liver failure, renal insufficiency, respiratory distress, congestive heart failure (NYHA III-IV), unstable angina, myocardial infarction, significant arrhythmia,
- Known deficiency in dihydropyrimidine dehydrogenase,
- Known Gilbert's syndrome,
- Total bilirubin level >1.5x the upper limit of normal (ULN); AST and/or ALT >5x ULN; TP <50%;
- Neutrophils <1.5x109/l, platelets <100x109/l, hemoglobin <10 g/dl,
- Chronic uncontrolled diarrhea, unresolved intestinal occlusion or subocclusion,
- History of anaphylactic reaction or known intolerance to atropine (sulfate) or to loperamide or to antiemetics administered in association with Folfiri.
3) Relating to bevacizumab:
- Uncontrolled wound and important surgery within the last 28 days
- Uncontrolled brain metastases (by local treatment),
- All uncontrolled progressive disease within 1 month prior to randomization: grade 3-4 gastrointestinal bleeding (peptic ulcer, erosive esophagitis or gastritis), infectious disease or intestinal inflammation, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event,
- Uncontrolled high blood pressure, defined as a systolic blood pressure >140 mmHg or diastolic pressure >90 mmHg,
- Patients receiving anticoagulant treatment with an unstable dose of a vitamin K antagonist treatment, and/or having an abnormal INR (>3) in the four weeks before the randomization,
- Verified proteinuria above or equal to 1g/24 hours measured from 24 hours of urine if the urinary protein dipstick control is above or equal to 2+,
- Creatinine clearance (MDRD) <50 ml/min.
- Hypersensitivity to the active substance or to any of the excipients.
- Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Show that, after the failure of a first-line chemotherapy using platinum-etoposide, the combination Folfiri-bevacizumab allows significant prolongation of overall survival in adult patients with GEP-NEC;Secondary Objective: - Objective response rate (complete response + partial response),<br>- Response duration<br>- Disease control rate (objective response + stable disease),<br>- Progression-free survival,<br>- Tolerance, <br>- Biochemical response (LDH, NSE, chromogranin A)<br>;Primary end point(s): Proportion of patients alive 6 months after the beginning of treatment;Timepoint(s) of evaluation of this end point: 6 months after beginning of treatment
- Secondary Outcome Measures
Name Time Method