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

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.

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

Study Overview

• Status: Completed
• Conditions: Angiosarcoma
• Intervention / Treatment: Drug: Paclitaxel; Drug: Bevacizumab

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

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Clermont Ferrand, France, 63011
    • Centre Jean Perrin
  • Dijon, France, 21079
    • Centre GEORGES FRANÇOIS LECLERC
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Montpellier, France, 34298
    • Centre Val D'Aurelle
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75005
    • Institut Curie
  • SAINT PRIEST en JAREZ, France, 42270
    • Institut De Cancerologie De La Loire
  • Saint Herblain, France, 44805
    • Centre René Gauducheau
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Villejuif, France, 94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm A : Paclitaxel; administration of paclitaxel drug during cycle of 28 days (6 cycles Max) + blood sample on day 1, 8, 15, 29 and 57	Drug: Paclitaxel; Day 1, 8 and 15 : Paclitaxel 90 mg/m², IV over 1h, during 6 cycles (1 cycle = 28 days); Other Names: Taxol
Other: Arm B : Paclitaxel + Bevacizumab; 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	Drug: Paclitaxel; Day 1, 8 and 15 : Paclitaxel 90 mg/m², IV over 1h, during 6 cycles (1 cycle = 28 days); Other Names: Taxol; Drug: 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; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Tolerance	According to NCI-CTCAE v4.0	during the study
Correlation between efficacity and serum expression of anti angiogenic factors	Blood samples at different times	Day 1, 8, 15, 29 and 57
Correlation between efficacity and beta-tubuline III expression in tissue	Paraffin blocks	At baseline

Collaborators and Investigators

• Sponsor: Centre Oscar Lambret
• Collaborators: French Sarcoma Group; Study Group of Bone Tumors
• Investigators: Principal Investigator: Nicolas PENEL, MD, PhD, Centre Oscar Lambret

Publications and helpful links

General Publications

• Lebellec L, Bertucci F, Tresch-Bruneel E, Ray-Coquard I, Le Cesne A, Bompas E, Blay JY, Italiano A, Mir O, Ryckewaert T, Toiron Y, Camoin L, Goncalves A, Penel N, Le Deley MC. Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial. BMC Cancer. 2018 Oct 11;18(1):963. doi: 10.1186/s12885-018-4828-1.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2010
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): January 29, 2019

Study Registration Dates

• First Submitted: February 23, 2011
• First Submitted That Met QC Criteria: February 23, 2011
• First Posted (Estimate): February 24, 2011

Study Record Updates

• Last Update Posted (Actual): May 30, 2019
• Last Update Submitted That Met QC Criteria: May 29, 2019
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: bevacizumab; Paclitaxel; Angiosarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Vascular Tissue; Hemangiosarcoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Paclitaxel; Bevacizumab
• Other Study ID Numbers: ANGIO-TAX-PLUS-0906

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No