An open-label, randomized, multicenter, phase II, comparative, exploratory study on neoadjuvant treatment with trastuzumab plus docetaxel versus trastuzumab plus docetaxel plus bevacizumab according to Positon Emission Tomography (PET) value modification in patients with early stage HER2 positive breast cancer - AVATAXHER

Phase 1

• Conditions: early stage HER2 positive breast cancer; MedDRA version: 12.0Level: PTClassification code 10057654Term: Breast cancer female

• Registration Number: EUCTR2009-013410-26-FR
• Lead Sponsor: ROCHE SAS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12-28
• Last Update Posted: 5 June 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 156

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

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) < 1.2 x 109/L
2. Platelet count <100 x 109/L
3. Haemoglobin < 9.00 g/dL
4. Impaired liver function: Serum (total) bilirubin: > 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 < 50 mL/min according to the Cockroft and Gault formula
6. 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
7. Patients not receiving anticoagulant medication and having an International
Normalized Ratio (INR) >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

Study & Design

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