An Open-Label, Randomized, Multicenter, Phase II, Non Comparative, Exploratory Study on Neoadjuvant Treatment With Trastuzumab Plus Docetaxel Plus Bevacizumab According to Positon Emission Tomography (PET) Value Modification in Patients With Early Stage HER2 Positive Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 152
- 试验地点
- 28
- 主要终点
- Percentage of Participants With Pathological Complete Response as per Chevallier's Classification as Reviewed by an Independent Committee
研究概览
简要总结
This randomized study will assess the effect of adding bevacizumab to trastuzumab plus docetaxel in neoadjuvant therapy in participants with early stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. After 2 cycles of trastuzumab and docetaxel once every 3 weeks, participants with a response (change in standard uptake value [SUV]) of less than (<) 70 percent (%) on Positron Emission Tomography (PET) will be randomized in a 2:1 ratio to receive Cycles 3 to 6 of trastuzumab (6 milligrams per kilogram [mg/kg]) and docetaxel (100 milligrams per square meter [mg/m^2]) with or without bevacizumab (15 mg/kg). Participants with a response of greater than or equal to (>/=) 70% will receive trastuzumab plus docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery (as per investigator's discretion) after Cycle 7 and between 4 and 6 weeks after the treatment perfusion of Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy (starting from 4-8 weeks after surgery during 4-6 weeks, according to site's standard practice) with or without hormonal therapy (mandatory if positive hormone receptors). Participants will be followed for up to 5 years from start of neoadjuvant treatment.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Participants with early stage HER2-positive breast cancer
- •Scheduled to receive neoadjuvant therapy with the objective of conservative surgery
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
排除标准
- •Participants with partial or total lobular carcinoma
- •Participants with inflammatory breast cancer
- •Previous treatment with chemotherapy, radiation therapy or hormonal therapy for breast cancer
- •Previous history of cancer (other than curatively treated basal and squamous cell carcinoma of the skin and/or in situ carcinoma of the cervix) relapsing within the 5 years before study entry or in situ contralateral breast carcinoma
研究组 & 干预措施
Trastuzumab, Docetaxel, and Bevacizumab
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel along with bevacizumab in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the bevacizumab infusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Bevacizumab (Drug)
Trastuzumab, Docetaxel, and Bevacizumab
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel along with bevacizumab in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the bevacizumab infusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Docetaxel (Drug)
Trastuzumab, Docetaxel, and Bevacizumab
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel along with bevacizumab in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the bevacizumab infusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Trastuzumab (Drug)
Trastuzumab, Docetaxel, and Bevacizumab
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel along with bevacizumab in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the bevacizumab infusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Surgery (Procedure)
Trastuzumab, Docetaxel, and Bevacizumab
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel along with bevacizumab in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the bevacizumab infusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Radiotherapy (Radiation)
Trastuzumab, Docetaxel, and Bevacizumab
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel along with bevacizumab in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the bevacizumab infusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Hormonal Therapy (Drug)
Trastuzumab and Docetaxel
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Docetaxel (Drug)
Trastuzumab and Docetaxel
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Trastuzumab (Drug)
Trastuzumab and Docetaxel
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Surgery (Procedure)
Trastuzumab and Docetaxel
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Radiotherapy (Radiation)
Trastuzumab and Docetaxel
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Hormonal Therapy (Drug)
Trastuzumab and Docetaxel (Standard Regimen)
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of >/=70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Docetaxel (Drug)
Trastuzumab and Docetaxel (Standard Regimen)
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of >/=70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Trastuzumab (Drug)
Trastuzumab and Docetaxel (Standard Regimen)
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of >/=70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Surgery (Procedure)
Trastuzumab and Docetaxel (Standard Regimen)
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of >/=70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Radiotherapy (Radiation)
Trastuzumab and Docetaxel (Standard Regimen)
Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of >/=70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.
干预措施: Hormonal Therapy (Drug)
结局指标
主要结局
Percentage of Participants With Pathological Complete Response as per Chevallier's Classification as Reviewed by an Independent Committee
时间窗: After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
次要结局
- Percentage of Participants With Pathological Complete Response According to Chevallier's Classification as per Local Procedures(After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days))
- Percentage of Participants With Pathological Complete Response According to Sataloff's Classification as Reviewed by an Independent Committee(After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days))
- Percentage of Participants With Ultrasound Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)(Neodajuvant treatment period (21 weeks))
- Percentage of Participants With Conservative Surgery Post Neoadjuvant Treatment(Week 20 (between Day 28 and Day 35 after the Cycle 6, cycle length=21 days))
- Local Relapse-Free Interval (LRFI) According to Modified RECIST Criteria(From baseline to occurrence of relapse/disease or death of any cause (up to 5 years))
- Disease-Free Survival (DFS) According to Modified RECIST Criteria(From baseline to occurrence of relapse/disease or death of any cause (up to 5 years))
- Distant Disease-Free Interval (DDFI) According to Modified RECIST Criteria(From baseline to occurrence of relapse/disease or death of any cause (up to 5 years))
- Overall Survival(Baseline up to occurrence of death (up to 5 years))
- Percentage of Participants With Adverse Events(Baseline up to 5 years)