early stage HER2 positive breast cancer MedDRA version: 12.0 Level: PT Classification code 10057654 Term: Breast cancer female
Conditions
Interventions
Trade Name: AVASTIN
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Current Sponsor code: Ro4876646
Other descriptive name: rhuMAB
Sponsors
ROCHE SAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General inclusion criteria: 1. Woman 2. Age = 18 years 3. Patient must have signed a written informed consent form prior to any study specific screening procedures 4. Patients able to undergo a pre-treatment PET and a second course PET 5. Affiliated to the ”Sécurité Sociale” or beneficiary to such a regimen Disease specific inclusion criteria: 1. Patient with invasive, T2 or T3 and histologically confirmed breast cancer, who is scheduled to receive neoadjuvant therapy with the objective of conservative surgery (see Appendix 2) 2. Nx ou N0 or N1 (see Appendix 2) 3. HER2 positive (needle core biopsy only) assessed by ICH [HER2 +++ or HER2 ++ (and FISH or CISH + or SISH+)] or FISH + or CISH + or SISH +, on the basis of ASCO 2007 criteria (see Appendix 3) 4. Known hormone receptors status. 5. Performance status (ECOG Scale, see Appendix 4): 0, 1 or 2 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
Exclusion criteria: Cancer related Exclusion Criteria: 1. Partially or totally lobular carcinoma 2. Inflammatory breast cancer 3. Bifocal and/or bilateral tumor 4. Metastases 5. Previous treatment with chemotherapy, radiation therapy or hormonal therapy for breast tumor 6. 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. Haematological, biochemical and organ function: 1. Absolute neutrophil count (ANC) 1.5 x ULN (except if Gilbert hemolysis); AST or ALT: > 2.5 x ULN 5. Inadequate kidney function: serum creatinine > 1.25 ULN or creatinine clearance 1.5 or an activated Partial Thromboplastin Time (aPTT) or PTT >1.5 x ULN within 7 days prior to first study treatment (4). Note: Patients receiving full dose oral or parenteral anticoagulants may be included in the study as long as anticoagulant dosing has been stable for at least two weeks prior to study entry and the appropriate coagulation monitoring tests are within local therapeutic limits (4). Other Study Drug Related Exclusion Criteria 1. 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. 2. History of thrombotic disorders within the last 6 months prior to enrolment (i.e. cerebrovascular accident, transient ischaemic attacks). 3. History of abdominal fistula, tracheo-oesophageal fistula or any grade 4 non gastrointestinal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment. 4. History or evidence of inherited bleeding diathesis or coagulopathy. 5. Non-healing wound, active peptic ulcer or bone fracture. 6. Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrollment or anticipation of the need for major surgery during study treatment. 7. Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion (4). 8. 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 (4). General Exclusion Criteria 1. Severe resting dyspnea due to complications or oxygen dependency 2. 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 (see Appendix 5), serious cardiac arrhythmia requiring medication during the study which might interfere with regularity of the study treatment or not controlled by medication. 3. LVEF = 50% by local definition using MUGA or echo cardiogram 4. Patient suffering fro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the complete pathological response rates (evaluation according to Chevallier’s criteria, review by an independent Committee) between the two randomized arms (neoadjuvant regimens) in patients with a relative change in [18F]-FDG tumoral uptake < 70%;Secondary Objective: For all patients (Arms A, B and Standard) : -to describe the complete pathological response rates evaluated according to local procedures, - to describe the ultrasound response rate, rate of conservative surgery, disease-free survival, distant disease-free survival, local relapse-free survival and overall survival, - to assess the role of PET in early detection of pathological response, - to search for predictive factors of response to treatment [on the basis HER2/RH status, pathological complete response, imaging results (PET and mammary DCE-US), and pharmacokinetics, immunology, and pharmacogenetics (only for patients who agree to participate, specific consent)] study results], - to assess the safety according to CTC-AE v 4.0. For the randomized Arms A and B (patients with ? SUV < 70%) : to search for predictive factors of response to treatment on the basis of angiogenesis biomarkers (biology and imaging).;Primary end point(s): Pathological complete response rates. pCR will be evaluated post-surgery (Chevallier criteria) by an independent Committee (for all patients). The patients with ? SUV < 70% will be randomized (2:1) to received either docetaxel + trastuzumab + bevacizumab or docetaxel + trastuzumab. 84 patients (docetaxel + trastuzumab + bevacizumab: 56 patients; docetaxel + trastuzumab: 28 patients) will allow to detect a difference between the two treatment groups of 30% in pCR rates in favor of docetaxel + trastuzumab + bevacizumab Arm with a power of 80% assuming a pCR rate of 10% in either docetaxel + trastuzumab Arm and a two sided type I error of 5%. According to the hypothesis that 60% of patients will have a ? SUV < 70% before | — |
Countries
France
Outcome results
None listed