Clinical trial NCT01303497: Efficacity of Weekly Paclitaxel in Association or Not With Bevacizumab in Metastatic or Locally Advanced Angiosarcomas
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Angiosarcoma
Keywords: Angiosarcoma
Paclitaxel
bevacizumab
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
Collaborators: name: French Sarcoma Group
name: Study Group of Bone Tumors
First posted: 2011-02-24
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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+, 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

Primary outcomes:
measure: Progression free rate after 6 months of treatment
timeFrame: after 6 months of treatment
Secondary outcomes:
measure: Objective response at 3, 6, 9 months of treatment
timeFrame: at 3, 6, 9 months of treatment
measure: Median progression-free rate
timeFrame: an average time period of 1 year
measure: Global median survival
timeFrame: an average time period of 18 months
measure: Tolerance
timeFrame: during the study
measure: Correlation between efficacity and serum expression of anti angiogenic factors
timeFrame: Day 1, 8, 15, 29 and 57
measure: Correlation between efficacity and beta-tubuline III expression in tissue
timeFrame: At baseline
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Montpellier
country: France
facility: Centre Val d'Aurelle
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Saint Herblain
country: France
facility: Centre René Gauducheau
city: SAINT PRIEST en JAREZ
country: France
facility: Institut de Cancérologie de la Loire
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Oscar Lambret
name: Nicolas PENEL, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.