efficacity of weekly paclitaxel in association or not with bevacizumab in metastatic or locally advanced angiosarcomas

Conditions: Angiosarcoma

Summary: efficacity of paclitaxel in association or not with bevacizumab in treatment of angiosarcoma

randomization is stratified : * angiosarcoma in irradiated region : yes / no * visceral angiosarcoma : yes / no all patient will received a maximum of 6 cycles of weekly paclitaxel (arm a and b) in association or not with bevacizumab (armb). 1 cycle = 28 days treatment by bevacizumab is to continue beyond the 6th cycle, until disease progression or unacceptable toxicity arm a and b: day 1, d8 and d15 paclitaxel : 90 mg/m², iv weekly with premedication arm b : day 1 and d15 bevacizumab : 10 mg/kg and then, bevacizumab : 15 mg/kg/3 weeks until disease progression or unacceptable toxicity

Eligibility criteria:
inclusion criteria: * angiosarcoma histologically proven * metastatic or locally advanced and not accessible to surgery treatment * measurable tumor with at least 1 measurable lesion, according to recist * for angiosarcoma in irradiated region, absence of clinical arguments of progression of the tumor prior treated by radiation * at least 28 days since the previous treatment (systemic or major surgery) * performance status (ecog) ≤ 1 * man or woman \>= 18 years * polynuclear neutrophils \>1500/mm3, platelets \> 100 000/ mm3, hemoglobin \> 9.0 g/dl * total bilirubin ≤ 1.5 x usl, ast and alt ≤ 2.5 x usl (or ≤ 5 if hepatic metastasis ) * serum creatinin ≤ 1.5 x usl or clearance calculated \> 50 ml/mn (cockcroft formulae) * absence of hematuria on dipstick * proteinuria on dipstick \ 2, the 24 hours proteinuria must be \< 1g * albumin \> 35 g/l and lymphocytes \> 700/mm3 attesting a life expectancy \> 3 months * normal cardiac function : lvef ≥ 50% * normal coagulation test : inr ≤ 1.5 and tca ≤ 1.5 x usl within 7 days before inclusion * systolic bp ≤ 150 mmhg and diastolic bp ≤ 100 mmhg * negative pregnancy test for women of reproductive potential(within 7 days before treatment start) * effective contraceptive methods for male and female (if applicable) during the period of treatment and until the 6 months after the last administration of bevacizumab * adequate central veinous access * patient covered by government health insurance * informed consent form signed by the patient exclusion criteria: * patients that have received more than 2 regimens of chemotherapy whatever the indication * kaposi's sarcoma, hemangio-endothelioma, hemangio-pericytoma (malignant solitary fibrous tumor) * surgery (except the diagnostic biopsy) or radiotherapy within the past 4 weeks before inclusion, except antalgic radiotherapy * uncontrolled, active peptic ulcer, * other malignant evolutive tumor * previous thrombotic or hemorrhagic disorders * clinically significant cardiovascular disease (stroke within 6 months prior inclusion, unstable angina, heart failure, myocardial infarction, arrhythmia requiring treatment) * anticoagulant treatment for curative aim within 10 days before beginning of treatment (oral or parenteral administration), aspirin \> 325 mg/day, or plavix or a thrombolytic (thrombolytics for preventive use is permitted) or anti-platelet (dipyridamol, ticlopidine, clodiprogel, cilostazol) * chronic treatment(more than 15 days) by every ains including aspirin \> 325 mg/j * currently active bacterial or fungus infection (grade \> 2 ctcae v4.02) * known hiv1, hiv2, hepatitis b or hepatitis c infections * presence of known meningeal or brain metastasis * epilepsy requiring the use of anti-epileptic * previous organ transplant * peripheral stem cell transplantation within 4 months prior to inclusion in the study * using of drugs affecting the biological response, for example g-csf, within the 3 weeks before inclusion * kidney dialysis patient * clinically significant neuropathy (grade\> 2 ctcae v4.02) * any circumstance that could jeopardise compliance or proper follow-up during the trial * pregnant or nursing women. women should not breastfeed for at least 6 months after the last administration of bevacizumab * constitutional or acquired coagulopathy * uncontrolled hypertension (sbp\> 150 mmhg or dbp\> 100 mmhg) * known hypersensitivity to paclitaxel or to one of its excipients (cremophor el, to bevacizumab components, to products of chinese hamster ovary cells (cho) or other recombinant human or humanized antibodies * patients unable to undergo trail medical follow-up for geographical, social or psychological reasons * patient refusal of ambulatory care

Keywords: angiosarcoma paclitaxel bevacizumab