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

Study Overview
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Brief Summary
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To compare continuing bevacizumab + paclitaxel or switching to bevacizumab + endocrine maintenance therapy followed by bevacizumab + paclitaxel, after 1st line induction therapy with bevacizumab + paclitaxel in ER+HER2- advanced or metastatic breast cancer.

Detailed Description
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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).

Official Title
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Bevacizumab Plus Paclitaxel Optimization Study With Interventional Maintenance Endocrine Therapy in Advanced or Metastatic ER-positive HER2-negative Breast Cancer -BOOSTER Trial, a Multicenter Randomized Phase II Study-

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Bevacizumab
* Drug: Letrozole
* Drug: Anastrozole
* Drug: Exemestane
* Drug: Fulvestrant
* Drug: Goserelin
* Drug: leuprorelin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>weekly paclitaxel + bevacizumab | Drug: Paclitaxel<br> <br> * Other names: Taxol;Drug: Bevacizumab<br> <br> * Other names: Avastin;|
| Experimental: Arm B<br>endocrine therapy* + bevacizumab then back to weekly paclitaxel + bevacizumab therapy (*Letrozole, Anastrozole, Exemestane, Fulvestrant, LHRH Analogs + Aromatase inhibitors.) | Drug: Paclitaxel<br> <br> * Other names: Taxol;Drug: Bevacizumab<br> <br> * Other names: Avastin;Drug: Letrozole<br> <br> * Other names: Femara;Drug: Anastrozole<br> <br> * Other names: Arimidex;Drug: Exemestane<br> <br> * Other names: Aromasin;Drug: Fulvestrant<br> <br> * Other names: Faslodex;Drug: Goserelin<br> <br> * Other names: Zoladex;Drug: leuprorelin<br> <br> * Other names: Leuplin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to failure of strategy (TFS) |  | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2y Overall Survival rate |  | 3.5 years | 
| Overall Survival |  | 3.5years | 
| Progression Free Survival(PFS) |  | 2.5years | 
| QOL |  | 2.5years | 
| Biomarker(IMPACT assay Chips, whole blood, tumor tissue, Serum) | vascular endothelial growth factor(VEGF)-A, VEGFR-2, VEGF-C, platelet derived growth factor(PDGF)-C, Soluble fms-like tyrosine kinase-1, VEGFR-3, Interleukin(IL)-8, Basic Fibroblast Growth Factor(FGFb), placental growth factor(PLGF), E-Selectin, intercellular adhesion molecule(ICAM)-1, neuropilin of Tumor tissue, single nucleotide polymorphism(SNP):VEGFR-1 and VEGF of whole blood DNA, angiotensin(ANG) and Apelin of serum. | 2.5years | 
| Safety(Collection of adverse events) |  | 2.5years |