AB12008

Etude de phase 2, prospective, multicentrique, en ouvert, avec allocation centralisée, controlée, visant à comparer l'efficacité et la tolérance de MASATINIB en association avec GEMCITABINE versus GEMCITABINE seule, chez des patientes atteintes d'un cancer de l'ovaire epithelial metastatique/ avancé en 2eme ligne de traitement réfractaire à une premiere ligne de traitement avec sels de platine ou en 3eme ligne de traitement

Critères d'inclusion :

Female patient, with histologically or cytologically confirmed advanced / metastatic epithelial ovarian cancer either :
- refractory to first line platinum treatment (defined as progressive disease while receiving or persistent disease after platinum-based therapy, according to GOG), or
- candidate to third line treatment.

Patient has recovered of all acute toxic side effects of prior therapy or surgical procedures to grade ≤ 1 National Cancer Institute-Common Toxicity Criteria (NCI-CTCAE v4.02), except for the laboratory Values

Patient has at least one target lesion that can be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (RECIST)

ECOG Performance status ≤ 2

Patient with adequate organ function

Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
Haemoglobin ≥ 10 g/dl
Platelets (PLT) ≥ 75 x 109/L
AST/ALT ≤ 3 x ULN (≤ 5 x ULN in case of liver metastases)
Gamma GT ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastases)
Bilirubin ≤ 1.5x ULN (≤ 3xULN in case of liver metastases)
Normal Creatinine or if abnormal creatinine, creatinine clearance ≥ 50 mL/min (Cockcroft and Gault formula)
Albumin > 1 x LLN
Urea ≤ 2 x ULN
Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is ≥ 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours

Patient with life expectancy > 3 months

Patient weight > 40 kg and BMI > 18

Female patient ≥ 18 years

Patient with nutritional risk index (NRI) ≥ 83.5, i.e. with no or moderate malnutrition; NRI is calculated as follows: NRI = 1.519 x serum albumin level + 0.417 x (current weight / basic weight) x 100

Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two 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.

Patient able and willing to comply with study visits and procedures as per protocol

Patient is able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures performed. If the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable, the designated legal guardian must sign the informed consent

Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity during the first 2 months of treatment

Patient affiliated to a social security regimen

Critères de non inclusion :

Patient intolerant to gemcitabine or having received gemcitabine as a second line therapy

Patient who has not recovered from any significant treatment toxicities prior to baseline (≥Grade 2)

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 (atrioventricular block 2 and 3, sino-atrial block)
Syncope without known aetiology within 3 months
Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic

Hypertension

Pregnant or nursing female patient

Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis

Patient treated for a cancer other than epithelial ovarian cancer within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ

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