PAZOPANIB Efficacy and Tolerance in Desmoids Tumors

Inclusion Criteria

• Written consent;
• Age ≥ 18 years;
• ECOG ≤ 1;
• Histologically confirmed desmoid tumor;
• Disease progression before the patient's inclusion : completion of two similar imaging obtained within 6 months apart (a tolerance of 6 weeks is accepted)
• Measurable target lesion (RECIST criteria) ;
• Left ventricular ejection fraction (MUGA or ECHO) within the normal;
• Normal hematological, renal and liver functions :
• Hemoglobin ≥ 9 g / dl; neutrophils ≥ 1.5 x 109 / l; platelets ≥ 100 x 109 / l; prothrombin time or INR1 ≤ 1.2 ULN or activated partial thromboplastin time ≤ 1.2 ULN;
• Amino alanine transferase and aspartate amino transferase ≤ 2.5 ULN;
• Total bilirubin ≤ 1.5 ULN;
• Creatinine ≤ 1.5 mg/dl or, if creatinine> 1.5 mg/dl, Creatinine clearance ≥ 50 m/min;
• Urinary protein / urinary creatinine (Pu / Cu) 480 ms;
• History of cardiovascular disease in the last 6 months:
• Cardiac angioplasty;
• Myocardial infarction;
• Unstable angina;
• Bypass surgery;
• Symptomatic arterial disease.
• Congestive heart failure grade II, III or IV according to the New York Hearth Association (NYHA) classification;
• Uncontrolled arterial hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);
• History of stroke or transient ischemic attack, pulmonary embolism or deep vein thrombosis not treated, within 6 months;
• History of major surgery or trauma within 28 days prior the first day of treatment, or presence of a wound, fracture or non-healed ulcer;
• Evidence of active bleeding or bleeding tendency;
• Known endobronchial lesions and / or infiltrative lesions of the large vessels lung;
• History of hemoptysis of more than 2.5 ml in the eight weeks preceding the first day of chemotherapy;
• Pulmonary dysfunction, asthma, emphysema, chronic obstructive pulmonary bronchitis, pneumonia, pneumothorax, pulmonary contusion, hemothorax, distress acute respiratory syndrome, pulmonary fibrosis;
• Severe renal dysfunction;
• Severe hepatic dysfunction;
• History of psoriasis, rheumatoid arthritis, alcoholism, illness or chronic liver dysfunction;
• Any pre-existing severe or unstable medical or psychiatric condition, or other condition that may interfere with patient safety, the collection of its informed consent or adherence to treatment;
• Patient who refused or could not stop taking banned drugs for at least 14 days (or 5 half-lives of the drug) before the first day of start of chemotherapy and for the duration of the study;
• During cancer treatment:
• Radiotherapy, surgery or tumor embolization within 14 days before the 1st dose of pazobanib (arm A) or chemotherapy methotrexate, vinblastine (arm B);
• Chemotherapy, immunotherapy, biological treatment, experimental or hormone therapy within 14 days or 5 half-lives of medication before the first day of the pazopanib (arm A) or chemotherapy with methotrexate, vinblastine (arm B).
• History of cancer treatment toxicity> grade 1 and / or whose the intensity increases, outside of alopecia.
• Pregnancy and lactation
• Concomitant treatment which can't be interrupted or replaced and which is not indicated with methotrexate:
• Probenecid (alone or associated with sulfamethoxazole),
• Trimethoprim,
• Acetylsalicylic acid (for methotrexate doses above 20 mg per week with the acetylsalicylic acid and used at doses analgesics or antipyretics (≥ 500 mg per dose and/or 3 g per day),
• Phenylbutazone,
• Yellow fever vaccine.