Efficacy of Pazopanib in Gastrointestinal Stromal Tumors (GIST)

Inclusion Criteria: 1. Age ≥ 18 years. 2. Histologically confirmed, unresectable, metastatic and/or locally advanced GIST. 3. Progression or intolerance after treatment with at least imatinib (400 mg and 600/800 mg/d) then sunitinib at either 50mg/d on a 4w/6w schedule or 37.5mg/d continuous dosing. Intolerance is defined as documented grade 3 or higher toxicity requiring treatment interruption as documented in patient record. 4. Measurable disease according to RECIST v1.1. 5. Performance status ≤ 2 (WHO). 6. Left Ventricular Ejection Fraction (LVEF) in accordance with local standards. 7. Adequate organ system functions as defined below: * Haematologic parameters * Absolute neutrophil count (ANC) ≥ 1.5 G/L * Haemoglobin ≥ 9 g/dL * Platelets ≥ 100 G/L * Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.2 X upper limit of normal (ULN) NB: Subjects receiving anticoagulation therapy are eligible if INR is stable and within the recommended range. * Partial thromboplastin time (PTT) ≤ 1.2 X ULN * Hepatic parameters * Total bilirubin ≤ 1.5 X ULN * AST and ALT ≤ 2.5 X ULN * Renal parameters * Serum creatinine ≤ 1.5 mg/dL (133 µmol/L) or, if greater than 1.5 mg/dL: calculated creatinine clearance ≥ 50 mL/min * Urine Protein to Creatinine ratio (UPC) \< 1. If UPC ≥ 1, subjects must have a 24-hour urine protein value \<1g to be eligible. * Biochemical parameters * Kaliemia ≥ 1 X lower limit of normal (LLN) 8. a) Females of non-childbearing potential (i.e., physiologically incapable of becoming pregnant). b) Females of childbearing potential provided that they are not pregnant or lactating, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and who agrees to use adequate contraception. 9. Affiliation with a health insurance company. 10. Subjects must provide written informed consent Exclusion Criteria: 1. Prior malignant disease (other than GIST) within 3 years prior to entry, with the exception of in situ breast cell carcinoma or in situ carcinoma of the cervix or basocellular carcinoma or spinocellular carcinoma or bladder neoplasm, treated at least 6 months before and with no evidence of relapse. 2. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for patients with previously-treated CNS metastases, who are asymptomatic and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. CNS screening with computed tomography \[CT\] or magnetic resonance imaging \[MRI\] is required only if clinically indicated or if the subject has a history of CNS metastases. 3. Treatment with any of the following anti-cancer therapies: * radiation therapy, surgery or tumour embolisation within 14 days prior to the first dose of pazopanib OR * chemotherapy, biological therapy or investigational therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib. The analgesic radiation therapy is allowed (the irradiated lesions won't be chosen as target lesions during the evaluation) 4. Any ongoing toxicity from prior anti-cancer therapy that is \> Grade 1 followed and/or progressing in severity, except alopecia. 5. Other uncontrolled severe medical conditions. 6. Presence of uncontrolled infection. 7. Clinically significant gastrointestinal abnormalities * that may increase the risk for gastrointestinal bleeding. * that may affect absorption of investigational product. 8. Poorly controlled hypertension \[defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg\]. NB: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions at \> 1 hour interval; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be \<140/90 mmHg for the subject to be eligible to the study. 9. History of any cardiovascular pathology within the past 6 months. 10. Corrected QT interval (QTcB) \> 480 msec using Bazett's formula. 11. History of cerebrovascular accident, including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT), within the past 6 months. NB: Subjects with recent DVT treated with therapeutic anti-coagulating agents at least 6 weeks before inclusion are eligible. 12. Major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture or ulcer (procedures such as catheter placement are not considered to be major). 13. Evidence of active bleeding or bleeding diathesis. 14. Haemoptysis within 8 weeks before inclusion. 15. Platelet transfusion in the past 7 days. 16. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels. 17. Concomitant bilirubin and AST/ALT elevations above ULN. 18. Treatment with anti-vitamin K (LMWH are allowed). 19. Inability or unwillingness to discontinue prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study. 20. Inability to swallow. 21. Pregnant or lactating woman 22. Impossibility to comply with protocol constraints