A Multicenter, Randomized, Phase II Clinical Trial to Evaluate the Effect of Avastin in Combination With Neoadjuvant Treatment Regimens on the Molecular and Metabolic Characteristics and Changes in the Primary Tumors With Reference to the Obtained Responses in Patients With Large Primary HER2 Negative Breast Cancers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 150
- 试验地点
- 3
- 主要终点
- Percentage of Participants With Messenger Ribonucleic Acid (mRNA) Markers of Pathological Complete Response, as Assessed by Magnetic Resonance Imaging (MRI)
研究概览
简要总结
This study will evaluate the effect of bevacizumab in combination with chemotherapy or endocrine therapy, as preoperative treatment, in participants with HER2 negative breast cancer. Participants will be randomized to receive either chemotherapy (FEC100: Epirubicine 100 milligrams per square meter [mg/m^2], 5-fluorouracil 600 mg/m^2, and cyclophosphamide 600 mg/m^2] for 12 weeks followed by taxane (paclitaxel/docetaxel) for 12 weeks or endocrine therapy (an aromatase inhibitor] daily for 24 weeks) with or without bevacizumab (15 milligrams per kilogram [mg/kg] as intravenous [IV] infusion every 3 weeks up 24 weeks).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed, HER2-negative, men or pre- or post-menopausal women with primary operable adenocarcinoma of the breast, greater than or equal to (>=) 2.5 centimeters (cm) in size
- •Eastern Cooperative Oncology Group (ECOG)/world health organization (WHO) performance status less than or equal to (</=) 2
- •Normal baseline cardiac function (Left Ventricular Ejection Fraction [LVEF])
排除标准
- •Stage IV (metastatic) disease
- •Previous treatment for localized breast cancer less than (<) 24 months from diagnosis of present breast cancer
- •Other previous or current cancer except for basal cell cancer or in situ cervical cancer
- •Current or recent use of aspirin (greater than [>] 325 milligrams per day)
- •Clinically significant cardiovascular disease
研究组 & 干预措施
Chemotherapy
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks.
干预措施: Epirubicine (Drug)
Chemotherapy
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks.
干预措施: 5-Fluorouracil (5FU) (Drug)
Chemotherapy
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks.
干预措施: Docetaxel (Drug)
Chemotherapy
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks.
干预措施: Cyclophosphamide (Drug)
Chemotherapy
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks.
干预措施: Paclitaxel (Drug)
Chemotherapy and Bevacizumab
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks. Participants will also receive concurrent treatment with bevacizumab every 3 weeks for 24 weeks.
干预措施: Bevacizumab (Drug)
Chemotherapy and Bevacizumab
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks. Participants will also receive concurrent treatment with bevacizumab every 3 weeks for 24 weeks.
干预措施: Epirubicine (Drug)
Chemotherapy and Bevacizumab
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks. Participants will also receive concurrent treatment with bevacizumab every 3 weeks for 24 weeks.
干预措施: 5-Fluorouracil (5FU) (Drug)
Chemotherapy and Bevacizumab
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks. Participants will also receive concurrent treatment with bevacizumab every 3 weeks for 24 weeks.
干预措施: Cyclophosphamide (Drug)
Chemotherapy and Bevacizumab
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks. Participants will also receive concurrent treatment with bevacizumab every 3 weeks for 24 weeks.
干预措施: Paclitaxel (Drug)
Chemotherapy and Bevacizumab
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks. Participants will also receive concurrent treatment with bevacizumab every 3 weeks for 24 weeks.
干预措施: Docetaxel (Drug)
Endocrine Therapy
Participants will receive aromatase inhibitor therapy at discretion of the investigator for a period of 24 weeks.
干预措施: Aromatase Inhibitor (Drug)
Endocrine Therapy and Bevacizumab
Participants will receive aromatase inhibitor therapy at discretion of the investigator and concurrent treatment with bevacizumab for a period of 24 weeks.
干预措施: Aromatase Inhibitor (Drug)
Endocrine Therapy and Bevacizumab
Participants will receive aromatase inhibitor therapy at discretion of the investigator and concurrent treatment with bevacizumab for a period of 24 weeks.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Percentage of Participants With Messenger Ribonucleic Acid (mRNA) Markers of Pathological Complete Response, as Assessed by Magnetic Resonance Imaging (MRI)
时间窗: Baseline up to end of study treatment (approximately 24 weeks)
次要结局
- Percentage of Participants With New Lesions(Weeks 12 and 25)
- Percentage of Participants With Presence of Tumor Cells Close to Resection Margin(At Surgery (Between Weeks 24 and 25))
- Percentage of Participants With Objective Pathological Complete Response, as Assessed by Clinical Assessment(Baseline up to end of study treatment (approximately 24 weeks))
- Percentage of Participants With Tumor Deposit in Other Body Parts(At Surgery (Between Weeks 24 and 25))
- Tumor Free Resection Margin(At Surgery (Between Weeks 24 and 25))
- Pathological Tumor Size as Measure Using MRI(Baseline, Weeks 12 and 25)
- Percentage of Participants With Axillary Lymph Node Dissection Performed(At Surgery (Between Weeks 24 and 25))
- Pathological Tumor Size, as Assessed by Histopathological Examination(At Surgery (Between Weeks 24 and 25))
- Pathological Tumor Size as Measure Using Caliper(Cycles 1 to 10 (cycle length=21 days), and Week 25)
- Pathological Axilla Tumor Size as Measure Using Ultrasound(Baseline, Weeks 12 and 25)
- Percentage of Participants With Molecular Changes in Protein Kinase Expression(Baseline up to end of study treatment (approximately 24 weeks))
- Percentage of Participants With Type of Surgery(At Surgery (Between Weeks 24 and 25))
- Percentage of Participants With Lymph Node Involvement(Cycles 1 to 10 (cycle length=21 days), and Week 25)
- Percentage of Participants With Objective Tumor Response, as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)(Weeks 12 and 25)
- Percentage of Participants With Molecular Changes in Messenger Ribonucleic Acid (mRNA)/microRNA(miRNA)(Baseline up to end of study treatment (approximately 24 weeks))
- Percentage of Participants With Molecular Changes in Protein Expression(Baseline up to end of study treatment (approximately 24 weeks))
- Percentage of Participants With Single Nucleotide Polymorphism (SNP) Profiles Predicting Treatment Response(Baseline up to end of study treatment (approximately 24 weeks))
- Percentage of Participants With Treatment-Induced Changes in Tumor Cells as Determined by Number of Disseminated Tumor Cells in Bone Marrow(Baseline up to end of study treatment (approximately 24 weeks))
- Pathological Tumor Size as Measure Using Mamography(Baseline, Weeks 12 and 25)
- Pathological Breast Tumor Size as Measure Using Ultrasound(Baseline, Weeks 12 and 25)
- Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status(Screening, Cycles 1 to 10 (cycle length=21 days), and Week 25)
- Percentage of Participants With Treatment-Induced Changes in Tumor Cells as Determined by Number of Circulating Tumor Cells in Peripheral Blood(Baseline up to end of study treatment (approximately 24 weeks))