Bevacizumab Plus Paclitaxel Optimization Study With Interventional Aintenance Endocrine Therapy in Breast Cancer

This multicenter, randomized Phase II study of patients with advanced or metastatic estrogen receptor-positive human epidermal receptor type 2-negative breast cancer aims to compare two treatment strategies following induction therapy with 4-6 cycles of the combined use of weekly paclitaxel (wPTX) and bevacizumab (BV). In arm A, wPTX+BV is continued, while in arm B, wPTX is switched to maintenance endocrine therapy (hormone+BV) until disease progression, followed by wPTX+BV re-induction. The primary endpoint is time to failure of strategy, which is the time from randomization to a qualifying event (addition of a new agent not in the primary regimen, progressive disease during or after planned therapy, or death).

Inclusion criteria

• Histologically confirmed adenocarcinoma of the breast
• Female aged 20-75 years old at getting informed consent
• HER2 negative disease (IHC 0/1+ or 2+ with FISH negative)
• Documented estrogen receptor (ER) positive (>=1% by IHC)
• Inoperative locally advanced or metastatic breast cancer at enrolment
• Performance status (ECOG): 0-1 at enrolment
• Life expectancy of at least 3 months from enrolment
• No prior systemic therapy for recurrent breast cancer (excluding hormone therapy)
• No prior neo and/or adjuvant chemotherapy with taxane or adjuvant setting with a disease-free interval from completion of the taxane treatment to metastatic diagnosis of >= 12 months
• Patients with measurable lesion regarding with Response Evaluation Criteria in Solid Tumors(RECIST) criteria or who have evaluable lesion
• Patients with only bone lesion will be acceptable if the osteolytic lesion has a measurable soft tissue component by MRI or CT
• No influence on protocol treatment is considered in case prior therapy or examination.
• Adequate following organ function within 2 weeks before starting treatment. The latest examination results should be adopted and blood transfusion or treatment of hematopoietic factor drugs is not allowed 2 weeks before examination.

• Absolute neutrophil count >= 1500 /mm3 or white blood cell(WBC) count >= 3000 /mm3
• Platelets >=10 x 10000 /mm3
• Hb >= 9 g/dL
• Total bilirubin <= 1.5 mg/dL
• aspartate aminotransferase(AST) and alanine aminotransferase(ALT) <= 100 international unit(IU)/L
• Serum creatinine <= 1.5 mg/dL
• Urine dipstick for proteinuria <= 1+
• Written informed consent signed by patients before completing any treatment related procedure

Exclusion criteria

• Prior therapy with bevacizumab
• Active infection requiring intrvenous antibiotics at enrollment or infection with active HBV and/or HCV.
• Pregnancy, lactetion or in case of potentialy pregnancy women Not mind contraception in trial period.
• Known hypersensitivity to bevacizumab or paclitaxel
• History of hemoptysis (>= 2.5mL of bright red blood per episord).
• Use of disulfiram,cyanamide, carmofur or procarbazine Hydrochloride
• Patients with CNS metastases (except for not symptomatic)
• Persistent Grade >= 2 sensory neuropathy at enrollment
• Grade 3 >= hypertension (>= 2 use of antihypertensive drug)
• Evidence with arterial thromboembolism (Cerebral infarction, Myocardial infarction) or history within 1 year prior to enrollment.
• Evidence withvenous thromboembolism (deep vein thrombosis, pulmonary embolism) or history within 1 year prior to enrollment.
• History of GI perforation and/or serious abdominal fistula within 1 year prior to enrollment
• Cases that the investigator judged as inappropriate as the subject of this clinical study