Efficacity of Weekly Paclitaxel in Association or Not With Bevacizumab in Metastatic or Locally Advanced Angiosarcomas (ANGIO-TAX+)

Centre Oscar Lambret

Status and phase: Completed; Phase 2

Conditions: Angiosarcoma

Treatments: Drug: Paclitaxel; Drug: Bevacizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT01303497

ANGIO-TAX-PLUS-0906

Details and patient eligibility

About

Efficacity of Paclitaxel in association or not with Bevacizumab in treatment of angiosarcoma

Full 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

Enrollment: 70 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 2 patient groups

Arm A : Paclitaxel

Other group

Description:

administration of paclitaxel drug during cycle of 28 days (6 cycles Max) + blood sample on day 1, 8, 15, 29 and 57

Treatment:

Drug: Paclitaxel

Arm B : Paclitaxel + Bevacizumab

Other group

Description:

administration of paclitaxel drug during per cycle of 28 days (6 cycles Max) + Bevacizumab every two weeks during paclitaxel cycles then every 3 weeks during P cycles until disease progression or inacceptable toxicity + blood sample on day 1, 8, 15, 29 and 57

Treatment:

Drug: Paclitaxel

Drug: Bevacizumab