Trial of Neoadjuvant Endostar, Docetaxel and Epirubicin for Patients With Breast Cancer

Study Overview
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Brief Summary
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This study was designed to determine the efficacy and safety of neoadjuvant docetaxel and epirubicin (DE) with or without human recombinant endostatin (endostar) for breast cancer patients. The hypothesis of this protocol is that a combined angiogenesis inhibiting therapy to chemotherapy could further benefit breast cancer patients.

Detailed Description
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This is a multicenter, prospective, randomized, controlled phase Ⅲ clinical trial. A total of 800 patients with core-biopsy confirmed breast cancer, stage ⅡA to ⅢC, and to be treated with neoadjuvant systemic therapy are eligible for entry into this study. Patients will be allocated randomly to two groups to receive either 3 cycles of neoadjuvant DE and endostar or 3 cycles of neoadjuvant DE. All cases receive mammography, contrast-enhanced ultrasound (CEUS), magnetic resonance angiography (MRA), and positron emission tomography (PET) scanning pre- and post-neoadjuvant therapy, and then undergo surgical resection. The primary endpoint is clinical/pathological response. The clinical response will be evaluated according to RECIST criteria. The parameters of tumor metabolism and blood supply, as demonstrated by PET, MRA and CEUS, will be collected and analysed. The secondary endpoint is (1) the number of participants with adverse events, (2) quality of life scores, and (3) the number of adverse events reported during neoadjuvant therapy. In addition, the role of mammography, CEUS, MRA and PET for response evaluation, as well as the angiogenic profile and biological information involved in tumor response will be investigated.

Official Title
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Phase Ⅲ Trial of Neoadjuvant Recombinant Human Endostatin, Docetaxel and Epirubicin as First-Line Therapy in Patients With Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: docetaxel and epirubicin
* Drug: docetaxel and epirubicin plus endostatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed invasive breast cancer (core needle biopsy for breast cancer diagnosis and fine needle aspiration for lymph node metastasis diagnosis) Stage ⅡA-ⅢC Age 18-70 ECOG performance status 0-2 No evidence of distant metastasis No previous therapy Normal hematologic function left ventricular ejection fraction greater than 50 percent No abnormality of renal or liver function Written informed consent Exclusion Criteria: With allergic constitution or possible allergic reflection to drugs to be used in this study Any concurrent uncontrolled medical or psychiatric disorder History of severe heart diseases, including congestive heart failure, unstable angina, uncontrolled arrhythmia, myocardial infarction, uncontrolled high blood pressure, or heart valve disease. History of bleeding diathesis Being pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: docetaxel and epirubicin<br>DE chemotherapy alone | Drug: docetaxel and epirubicin<br>* docetaxel 75mg/m2, IV (in the vein) on day 1 of each 21 day cycle; epirubicin 75 mg/m2, IV (in the vein) on day 1 of each 21 day cycle, totally 3 cycles<br>* Other names: Epirubicin, Pfizer;|
| Experimental: docetaxel and epirubicin plus endostatin<br>chemotherapy plus endostatin | Drug: docetaxel and epirubicin plus endostatin<br>* docetaxel 75mg/m2, IV (in the vein) on day 1 of each 21 day cycle; epirubicin 75 mg/m2, IV (in the vein) on day 1 of each 21 day cycle; endostatin 7.5mg/m2, IV (in the vein) on 1st to 14th days of each 21 day cycle; every 3 weeks, totally 3 cycles<br>* Other names: Endostatin, Simcere-Medgenn (No. S20050088);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical/pathological response | The clincial response will be evaluated according to RECIST criteria. The parameters of tumor metabolism and blood supply, as demonstrated by PET, MRA and CEUS, will be collected and analysed. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | The number of participants with adverse events will be recorded and analysed. | 3 years | 
| Quality of life | Quality of life is scored using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Questionnaire (QLQ30) at study entry and prior to surgery. | 3 years | 
| Number of adverse events reported during neoadjuvant therapy | The adverse events during neoadjuvant therapy will be graded using the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 2.0. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, neoadjuvant chemotherapy, recombinant human endostatin (endostar), docetaxel, epirubicin