Angiosarcoma
Conditions
Keywords
Angiosarcoma, Paclitaxel, bevacizumab
Brief summary
Efficacity of Paclitaxel in association or not with Bevacizumab in treatment of angiosarcoma
Detailed description
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
Interventions
DRUGPaclitaxel
Day 1, 8 and 15 : Paclitaxel 90 mg/m², IV over 1h, during 6 cycles (1 cycle = 28 days)
DRUGBevacizumab
Bevacizumab until progression or inacceptable toxicity : * During the cycles of chemotherapy : Day 1 and D15 : 10 mg/kg,IV * After 6 cycles of chemotherapy : 15 mg/kg, IV
Sponsors
Centre Oscar Lambret
French Sarcoma Group
Study Group of Bone Tumors
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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+, if \>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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free rate after 6 months of treatment | after 6 months of treatment | Stable disease, complete response and partial response according to RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response at 3, 6, 9 months of treatment | at 3, 6, 9 months of treatment | Stable disease, complete response and partial response according to RECIST 1.1 |
| Median progression-free rate | an average time period of 1 year | Median time for both cohort between : * date of inclusion * date of clinical or radiological progression |
| Global median survival | an average time period of 18 months | Median time for both cohort between : * date of inclusion * date of death whatever the cause |
| Tolerance | during the study | According to NCI-CTCAE v4.0 |
| Correlation between efficacity and serum expression of anti angiogenic factors | Day 1, 8, 15, 29 and 57 | Blood samples at different times |
| Correlation between efficacity and beta-tubuline III expression in tissue | At baseline | Paraffin blocks |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORNicolas PENEL, MD, PhD
Centre Oscar Lambret
Outcome results
None listed