Bevacizumab in Combination With Chemotherapy in the Neo-adjuvant Setting for HER2 (-) Breast Cancer

This is an interventional treatment trial for Breast Cancer focused on measuring Early breast cancer, Primary operable breast cancer, HER2- negative, bevacizumab Read More

Inclusion Criteria:

• Female patients with histologic proven, corebiopsied, invasive ductal adenocarcinoma of the breast >2 cm in size and of any N stage (clinical and/or radiological T-stage > T1, including T4d), scheduled to receive preoperative chemotherapy.
• Age 18-70 years
• ECOG performance-status ≤1
• No prior or current neoplasm except for curatively treated non melanoma skin cancer, in situ carcinoma of the cervix
• No distant disease/secondary carcinoma
• Normal cardiac function

• Results of the following assessments at the time of inclusion must be available:

  1. bilateral Mammography (before enrolment)
  2. histology
  3. grading
  4. hormone-receptor-status
  5. HER2 status negative (is defined as FISH/CISH negative or IHC0 or IHC1+, or IHC2+ and FISH/CISH negative)

• Laboratory requirements (within 1 week before enrolment):

  1. Hematology: Neutrophils ≥ 1.5 x 109/l, Platelets ≥ 100 x 109/l, Hemoglobin>11 g/dl
  2. Hepatic function: Total bilirubin < 1 x ULN, SGOT and SGPT < 1.5 x ULN, Alkaline phosphatases < 1.5 x ULN. In case of abnormal values, the liver function tests have to be repeated within 3 days before study treatment.
  3. Renal function: Creatinine < 1 x ULN
  4. Urinalysis: Urine dipstick of 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 / 24 hours.
• Signed and dated Informed Consent before the start of specific protocol procedures
• If of childbearing potential, negative pregnancy test

Exclusion Criteria:

• Cytological only confirmation of diagnosis
• Lobular or other non-ductal types of breast cancer
• Pregnant, or lactating patients; patients of childbearing potential must implement adequate contraceptive measures during study participation
• Pre-existing motor or sensory neurotoxicity of a severity > grade 2 by NCI-CTC AE
• Preoperative local treatment for breast cancer (i.e. incomplete surgery, radiotherapy)
• Prior or concurrent systemic antitumor therapy
• Evidence of wound healing complications, bone fracture, ulcer or the presence of clinically significant peripheral vascular disease
• Clinically significant cardiac disease e.g. congestive heart failure.
• Other serious illness or medical condition-uncontrolled hypertension or high risk uncontrolled arrythmias -history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent-active uncontrolled infection-unstable peptic ulcer, unstable diabetes mellitus or other contraindication for the use of corticosteroids
• Known hypersensitivity reaction to the compounds or incorporated substances.
• Evidence of bleeding diathesis or coagulopathy
• The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR, or appropriate monitoring test is within therapeutic limits and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of randomization. Patients not receiving anti coagulant medication must have an INR ≤ 1.5 an aPTT ≤ 1.5 x ULN within 7 days of randomization.
• Ongoing treatment with aspirin (> 325mg / day) or other medications known to predispose to gastrointestinal ulceration.
• Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrolment.
• Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion
• Treatment with an investigational drug within 30 days prior to study entry.
• Legally incapacitated and/or other circumstances which make it undesirable for the subject to understand the nature, meaning and consequences of the clinical study