eoadjuvant Endocrine Treatment +/- Bevacizumab in postmenopausal Patients with Operable Primary, HER2-neu negative Breast Cancer (including Lobular Cancer) (I) not suitable for Chemotherapy or (II) unlikely to respond to Chemotherapy
- Conditions
- Postmenopausal women with histologically proven primary breast cancer of stages I-III scheduled for neoadjuvant endocrine treatment, N+/-, M0, HER2 negativeincluding patients with lobular breast cancer or patients with any breast cancer histology not suitable for chemotherapy or unlikely to respond to chemotherapy
- Registration Number
- EUCTR2010-024216-34-AT
- Lead Sponsor
- ABCSG (Austrian Breast & Colorectal Cancer Study Group)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 0
- Female Patients with histologically diagnosed hormone receptor positive (ER and/or PR positive ), HER2/neu negative (IHC < 2+ or FISH negative) operable breast cancer
1. Any condition excluding a patient from chemotherapy but not from endocrine treatment in combination with bevacizumab and therefore allowing patients to enter the study are:
(i) biological age
(ii) ECOG Performance status =2
(iii) normal or reduced hematopoietic reserve, but leukocytes >1,500/µl, platelets >1000,000/ µl and Hb =8 g/dl
(iv) Normal or reduced renal function but no necessity for dialysis
2. Stage I, II or Stage III (T2-T4a-c, N0-3, M0)
3. Postmenopausal status, defined as:
a) the patient is amenorrhoeic for > 12 months or
b) FSH and estradiol are in postmenopausal range or
c) the patient is 61 years of age or older.
4. No prior chemotherapy, radiotherapy, or endocrine therapy for invasive or non-invasive breast cancer.
5. Normal cardiac function must be confirmed by LVEF (MUGA scan or Echocardiography) within 4 weeks prior to randomization. The result must be above 50% .
6. Signed and dated informed consent
7. Willingness and ability to comply with treatment and all study related procedures
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
Concomitant conditions
1. Metastatic disease
2. Inflammatory carcinoma (T4d)
3. HER2neu positive breast cancer
4. Prior treatment for breast cancer
5. Active viral, bacterial or fungal infection
6. History of solid organ transplantation
7. CNS involvement by Breast Cancer or any evidence of spinal cord compression. Brain CT/MRI is only mandatory in case of clinical suspicion of CNS involvement by Breast Cancer
8. Prior malignancy (except adequately treated basal cell carcinoma of the skin, in situ cervical cancer, or any other cancer for which the patient has been in remission for at least 5 years)
9. Known hypersensitivity to study drug or its ingredients (i.e., hypersensitivity to Polysorbate 20, CHO cell products, or recombinant human antibodies)
10. Severe chronic obstructive pulmonary disease with hypoxemia
11. thrombosis unless resolved and under adequate control by anticoagulation (see 24)
12. Uncontrolled hypertension (>150mmHg and/or a diastolic >100 mmHg) or clinically significant (i.e. active) cardiovascular disease (CVA/stroke within <6 months prior to randomization) myocardial infarction within < 6 months prior to randomization, unstable angina pectoris, congestive heart failure (= NYHA Grade II), or serious cardiac arrhythmia requiring ongoing medication, NYHA = Grade II
13. Clinically significant, active peripheral vascular disease, serious non healing wound/ulcer, bone fracture, bleeding diathesis (history or evidence of inherited bleeding diathesis) and/or coagulopathy
14. History of active ulcer (within 1 year prior to randomization), abdominal fistula, gastrointestinal perforation, or intraabdominal abscess or concurrent therapy for treatment/prevention of ulcer
15. Evidence of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, or patient at high risk from treatment complications
16. Any co-existing medical or psychological condition that would compromise ability to give informed consent
17. Uncontrolled diabetes mellitus
Current treatment
18. Seizures requiring permanent anticonvulsant therapy
19. chronic daily treatment with corticosteroids (dose =10 mg/d methylprednisolone or equivalent) with the exception of inhaled steroids
20. chronic daily treatment with acetylsalicylic acid (aspirin or analogs >325 mg/day) or clopidrogel (>75 mg/day)
21. Major surgery, open biopsy or trauma within 28 days before randomization (fine-needle biopsies of breast tissue or lymph node are not considered major surgery), or the need for major surgery during the course of study treatment (adequate time delay of 6 weeks between last cycle of bevacizumab and surgery is considered in the design of the trial)
22. Current or recent (within the 30 days prior to randomization) treatment with another investigational drug or participation in another investigational therapeutic study
Laboratory (determined within 7 days prior to day 1 cycle 1)
23. Inadequate liver function, defined as:
- serum (total) bilirubin >1.5 x the upper limit of normal (ULN) for the institution
- AST/SGOT or ALT/SGPT >2,5 x ULN
- ALP >2.5 x ULN at baseline
24. Patients not receiving anticoagulant medication who have an International Normalized Ratio (INR) >1.5 or an activated partial thromboplastin time (aPTT) >1.5 x ULN within 7 days prior to first study treatment
25. Inadequate renal function (Proteinuria), d
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Assessment of efficacy of neoadjuvant bevacizumab in combination with exemestane in postmenopausal patients with hormone receptor positive (ER and/or PR positive) primary breast cancer, as measured by overall clinical response rates and determined by MRT. The overall clinical response (ORR) is defined as the percentage of patients with either a complete clinical response (CR) or a partial clinical response (PR).;Secondary Objective: Assessment of angiogenic response by DCE-MRT, downstaging rate to breast-conserving surgery, complete pathological response rate;Primary end point(s): Overall Response rate (CR, PR) by MRT
- Secondary Outcome Measures
Name Time Method