Study to evaluate 2 types of treatment as first line treatment (masitinib + gemcitabine or placebo + gemcitabine ) and 2 types of treatment as second line treatment (masitinib + FOLFIRI 3 or placebo + FOLFIRI 3) in the treatment of patients with with non resectable locally advanced or metastatic pancreatic cancer.

Conditions: on resectable locally advanced or metastatic pancreatic cancer after
MedDRA version: 18.0Level: PTClassification code 10033610Term: Pancreatic carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-002293-41-GR

Lead Sponsor: AB Science

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 549

Inclusion Criteria

First randomisation:
1. Histologically or cytologically confirmed adenocarcinoma of the pancreas, non resectable locally advanced or metastatic stage
2. Patient with pain related to the disease, as assessed by the investigator and the patient:
- Pain related to the disease as assessed by the investigator is defined as clinical and documented evaluation by the investigator during physical examinations at screening and/or baseline.
- Pain, as assessed by the patient is defined as at least one value out of two values > 20mm on Visual Analogue Scale at screening or baseline.
OR
Patient treated with opioid analgesics at dose = 1 mg/kg/day
OR
Patients with ‘genetic fingerprint of aggressiveness ACOX1 (DCt = 3.05)
3. Chemotherapy naïve patient for the advanced/metastatic disease
4. Documented decision justifying non eligibility for surgical resection.
5. Patient with measurable tumor lesions with longest diameter = 20 mm using conventional techniques or = 10 mm with spiral CT scan according to RECIST 1.1
6. Patient with ECOG = 1
7. Patient with adequate organ functions:
• Absolute neutrophils count (ANC) = 1.5 x 109/L
• Haemoglobin = 10 g/dL
• Platelets (PTL) = 75 x 109/L
• AST/ALT = 5x ULN
• Gamma GT = 5x ULN
• Bilirubin = 3x ULN
• Normal Creatinine or if abnormal creatinine, CrCl=50 mL/min (Cockcroft and Gault formula)
• Albumin > 1x LLN
• Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is = 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
8. Patient with life expectancy > 3 months
9. Male or female patient, age ?18 years
10. Patient with a BMI > 18 kg/m² and >40 kg
11. Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test at screening and baseline), who agrees to use two highly effective methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. These include:
• A documented placement of an intrauterine device (IUD) or system (IUS) and the use of a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository)
• Documented tubal ligation (female sterilization). In addition, a barrier method used with spermicidal should also be used
• Double barrier method: Condom and occlusive cap with spermicidal
• Any other contraceptive method with a failure rate of <1% per year
• Abstinence
12. Male patients must use medically acceptable methods of contraception if your female partner is pregnant, from the time of the first administration of the study drug until three months following administration of the last dose of study drug. These include:
• Condom;
• If the patient has undergone surgical sterilization (vasectomy with documentation of azoospermia) a condom should also be used.
Male patients must use two highly effective methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. These are:
• Condom and occlusive cap with spermicidal foam/gel/film/cream/suppository;
• Surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method used with spermicidal;
• The female partner uses oral contraceptives (combination oestrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier

Exclusion Criteria

First randomisation exclusion criteria:
1. Patient treated for a cancer other than pancreatic cancer within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ
2. Patient with no pain related to the disease (as defined in the inclusion criterion number 2) and no genetic fingerprint of aggressiveness
3. Patient with ECOG = 2
4. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
5. Patient presenting with cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension according to the judgement of the investigator, or symptomatic hypertension
6. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
7. Pregnant, intent to be pregnant, or nursing female patient
WASH OUT & PREVIOUS TREATMENT
1. Any anti-tumour therapy (any chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy) within 6 months prior to baseline
2. Treatment with any investigational agent within 4 weeks prior to baseline
3. Patients with an active infection requiring antibiotics within 14 days prior to registration

Second randomisation exclusion criteria:
1. Patient intolerant to masitinib
The patient is considered as intolerant to masitinib if he/she presented with a severe adverse event (grade = 3) due to the mechanism of action of masitinib (i.e. rash, nausea, vomiting or diarrhea) which led to interruption and/or dose reduction of first line treatment followed by a re-challenge of first line treatment leading to the same severe adverse event.
2. Patient having presented with disabling or life-threatening adverse event due to first line treatment