Multicenter, phase II trial assessing the efficacy and safety of bevacizumab (Avastin®) combined to trastuzumab (Herceptin®) based chemotherapy in patients with primary inflammatory HER2+ breast cancer - BEVERLY 2

• Conditions: Primary inflammatory HER2+ breast cancer; MedDRA version: 9.1Level: LLTClassification code 10065430Term: HER-2 positive breast cancer; MedDRA version: 9.1Level: LLTClassification code 10021974Term: Inflammatory breast cancer

• Registration Number: EUCTR2008-000783-16-FR
• Lead Sponsor: ROCHE SAS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05-05
• Last Update Posted: 19 January 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

•Patients must have signed a written informed consent form prior to any study specific screening procedures,
•Women ,
•18 years or older,
•Performance status 0 to 2,
•Life expectancy = 3 months,
•Able to comply with the protocol,
•Patient affiliated to the national Social Security” regimen or beneficiary of this regimen.
•Histologically confirmed breast cancer and confirmed inflammatory breast cancer defined as follows:
-T4d any N
-or PeV II IGR
-or PeV III IGR
-or skin biopsy with tumor emboles in the lymph vessels of the superficial derma.
•HER2 positive tumors by immunohistochemistry (IHC +++) or fluorescent/chromogenic in situ hybridization (FISH+ or CISH+)
•Hormone receptors status known.
•No metastases.
•Adequate hematologic function:
- Absolute neutrophil count = 1.2 x 10exp9/L AND
- platelets = 100 x 10exp9/L AND
- Hb = 9 g/dL
•Adequate liver function:
- Total bilirubin = 1.5 ULN unless elevation is due to Gilbert’s disease or similar syndrome involving slow conjugation of bilirubin AND
- ASAT < 2.5 ULN AND
- ALAT < 2.5 ULN
•Adequate kidney function:
-Serum creatinine = 1.25 ULN or Creatinine clearance = 50 mL/min according to the Cockroft and Gault formula AND
-Urine dipstick for proteinuria < 2+. Patients discovered to have = 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate = 1 g of protein in 24 hours
•Adequate coagulation function
-International normalized ratio (INR) = 1.5 (except for patients with prophylactic use of anticoagulant) and
- TCA = 1.5 x ULN within 7 days prior to enrolment.
•Adequate cardiac function
-Left ventricular ejection fraction (LVEF) = 55% (isotopic or ultrasound methods)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Incapacitated adults not able to give informed legal consent.
Pregnant or breast feeding women.
•Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective means of contraception
•Patient considered socially or psychologically unable to comply with the treatment and the required medical follow-up.
•Non inflammatory breast cancer with lymphatic skin permeation.
•Metastases.
Previous Cancer History
•Previous history of cancer (other than curatively treated basal and squamous cell carcinoma of the skin and/or in-situ carcinoma of the cervix) relapsing within the 5 years before study entry or in situ contralateral breast carcinoma.
•Patient previously treated with chemotherapy, radiation therapy or hormone therapy for a breast tumor.
•History or evidence of inherited bleeding diathesis or coagulopathy.
•Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg), with or without anti-hypertensive medication. Patients with high initial blood pressure are eligible if entry criteria are met after initiation or adjustment of antihypertensive medication.
•Clinically significant (i.e. active) cardiovascular disease, i.e. myocardial infarction within the last 6 months before inclusion, unstable angina, congestive heart failure NYHA Class = II, serious cardiac arrhythmia requiring medication during the study which might interfere with regularity of the study treatment or not controlled by medication.
•History of thrombotic disorders within the last 6 months prior to enrolment (i.e. cerebrovascular accident, transient ischaemic attacks).
•Severe resting dyspnea due to complications or oxygen dependency.
•Diabetic patient treated with oral antidiabetics or insulin with an underlying cardiopathy at ultrasound.
•Evidence of ongoing or active infection (requiring IV antibiotics), any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or increases the patient’s risk of treatment-related complications.

•Major surgery (including open biopsy), significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during study treatment.
•Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion.
•Non-healing wound, active peptic ulcer or bone fracture
•History of abdominal fistula, diagnosed with a tracheo-oesophageal fistula or any grade 4 non-gastrointestinal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment.
Current Medication
•Current or recent use of any non-steroidal anti inflammatory agent (aspirin > 325 mg/day), or anti aggregation agents (dypiridamole, ticlopidine, clopidogrel > 75 mg/day), within 10 days before the first administration of bevacizumab.
•Current or recent (within 10 days of first dose of bevacizumab) use of full dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes. Prophylactic use of anticoagulants is allowed.
•Patient with known contra-indication to radiotherapy.
•Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
•Vaccination by modified live vaccines, vaccination against yellow fever during study treatment period.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the rate of pathological complete response on surgical samples according to the Sataloff classification, by a centralized review, following a neoadjuvant treatment with bevacizumab combined to trastuzumab based chemotherapy in HER2+ inflammatory breast cancer;Secondary Objective: To Assess:<br><br>- Disease Free Survival (DFS).<br>- Recurrence free interval (RFI).<br>- Overall survival (OS).<br>- Safety according to CTC-AE v3.0. <br>- Cardiac safety based on NYHA classification. <br>- Predictive factors of efficacy (biology, pharmacokinetics, pharmacogenetics, pharmacogenomics, proteomics, imaging.)<br><br>;Primary end point(s): Rate of pathological complete response on surgical samples, according to Sataloff classification, by a centralized review, following a neoadjuvant treatment with bevacizumab combined to trastuzumab based chemotherapy in HER2+ inflammatory breast cancer