Efficacity of Weekly Paclitaxel in Association or Not With Bevacizumab in Metastatic or Locally Advanced Angiosarcomas

Angiosarcoma Clinical Trial

— ANGIO-TAX+  

Official title:

Phase II Study, Multicenter, Randomized, Stratified, Evaluating the Efficacity of Weekly Paclitaxel, With or Without Bevacizumab in the Treatment of Metastatic or Locally Advanced Angiosarcomas Not Accessible to Surgery Treatment.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01303497
• Other study ID #: ANGIO-TAX-PLUS-0906
• Status: Completed
• Phase: Phase 2
• Start date: September 10, 2010
• Est. completion date: January 29, 2019

Study information

• Verified date: January 2017
• Source: Centre Oscar Lambret
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: January 29, 2019
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Angiosarcoma

Intervention

Drug:
• Paclitaxel
Day 1, 8 and 15 : Paclitaxel 90 mg/m², IV over 1h, during 6 cycles (1 cycle = 28 days)
• Bevacizumab
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

Locations

Country	Name	City	State
France	Institut Bergonié	Bordeaux
France	Centre François Baclesse	Caen
France	Centre Jean Perrin	Clermont Ferrand
France	Centre Georges François Leclerc	Dijon
France	Centre Oscar Lambret	Lille
France	Centre Léon Bérard	Lyon
France	Centre Val d'Aurelle	Montpellier
France	Centre Antoine Lacassagne	Nice
France	Institut Curie	Paris
France	Centre René Gauducheau	Saint Herblain
France	Institut de Cancérologie de la Loire	SAINT PRIEST en JAREZ
France	Institut Claudius Regaud	Toulouse
France	Institut Gustave Roussy	Villejuif

Sponsors (3)

Lead Sponsor	Collaborator
Centre Oscar Lambret	French Sarcoma Group, Study Group of Bone Tumors

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free rate after 6 months of treatment	Stable disease, complete response and partial response according to RECIST 1.1	after 6 months of treatment
Secondary	Objective response at 3, 6, 9 months of treatment	Stable disease, complete response and partial response according to RECIST 1.1	at 3, 6, 9 months of treatment
Secondary	Median progression-free rate	Median time for both cohort between : date of inclusion; date of clinical or radiological progression	an average time period of 1 year
Secondary	Global median survival	Median time for both cohort between : date of inclusion; date of death whatever the cause	an average time period of 18 months
Secondary	Tolerance	According to NCI-CTCAE v4.0	during the study
Secondary	Correlation between efficacity and serum expression of anti angiogenic factors	Blood samples at different times	Day 1, 8, 15, 29 and 57
Secondary	Correlation between efficacity and beta-tubuline III expression in tissue	Paraffin blocks	At baseline