A Randomised, Multicentre, Multinational Phase II Study to Evaluate Pertuzumab in Combination With Trastuzumab, Given Either Concomitantly or Sequentially With Standard Anthracycline-based Chemotherapy or Concomitantly With a Non-anthracycline-based Chemotherapy Regimen, as Neoadjuvant Therapy for Patients With Locally Advanced, Inflammatory or Early Stage HER2-positive Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 225
- 主要终点
- Safety: Percentage of Participants With Symptomatic Cardiac Events as Assessed by the Investigator
研究概览
简要总结
This 3 arm study will assess the tolerability, safety and efficacy of 3 neoadjuvant treatment regimens in participants with locally advanced, inflammatory or early stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Before surgery, participants will be randomized to receive either A) 6 cycles of pertuzumab plus trastuzumab (Herceptin), with 5-fluorouracil/epirubicin/cyclophosphamide (FEC) for cycles 1-3 and docetaxel for cycles 4-6, or B) FEC for cycles 1-3 followed by pertuzumab plus trastuzumab with docetaxel for cycles 4-6, or C) 6 cycles of pertuzumab plus trastuzumab with docetaxel and carboplatin. Pertuzumab will be administered at a loading dose of 840 mg intravenously (iv), then 420 mg iv 3-weekly, trastuzumab at a loading dose of 8 mg/kg iv, then 6 mg/kg iv 3-weekly, docetaxel at 75 mg/m^2 iv, increased to 100 mg/m^2 iv 3-weekly, and FEC and carboplatin iv 3-weekly at standard doses. Following surgery participants will receive trastuzumab 6 mg/kg iv 3-weekly for a total of 1 year, as well as adequate chemo-, radio- and hormone therapy. Anticipated time on study treatment is 4-12 months, and target sample size is 200-300.
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
- •female participants, age >/=18 years
- •advanced, inflammatory or early stage unilateral invasive breast cancer
- •HER2-positive breast cancer
- •baseline left ventricular ejection fraction (LVEF) >/=55%
排除标准
- •metastatic disease (Stage IV) or bilateral breast cancer
- •previous anticancer therapy or radiotherapy for any malignancy
- •other malignancy, except for carcinoma in situ of the cervix, or basal cell carcinoma
- •clinically relevant cardiovascular disease
- •current chronic treatment with corticosteroids of >10mg methylprednisolone or equivalent
研究组 & 干预措施
T+P Concomitant Anthracycline-based chemotherapy
5-Fluorouracil, epirubicin with cyclophosphamide (FEC), trastuzumab (T) and pertuzumab (P) every three weeks for three cycles, followed by docetaxel, trastuzumab and pertuzumab every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
干预措施: Pertuzumab (Drug)
T+P Concomitant Anthracycline-based chemotherapy
5-Fluorouracil, epirubicin with cyclophosphamide (FEC), trastuzumab (T) and pertuzumab (P) every three weeks for three cycles, followed by docetaxel, trastuzumab and pertuzumab every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
干预措施: Trastuzumab (Drug)
T+P Concomitant Anthracycline-based chemotherapy
5-Fluorouracil, epirubicin with cyclophosphamide (FEC), trastuzumab (T) and pertuzumab (P) every three weeks for three cycles, followed by docetaxel, trastuzumab and pertuzumab every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
干预措施: FEC (Drug)
T+P Concomitant Anthracycline-based chemotherapy
5-Fluorouracil, epirubicin with cyclophosphamide (FEC), trastuzumab (T) and pertuzumab (P) every three weeks for three cycles, followed by docetaxel, trastuzumab and pertuzumab every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
干预措施: Docetaxel (Drug)
T+P Sequential Anthracycline-based chemotherapy
FEC every three weeks for three cycles, followed by docetaxel, trastuzumab (T) and pertuzumab (P) every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 21 as adjuvant therapy post-surgery.
干预措施: Pertuzumab (Drug)
T+P Sequential Anthracycline-based chemotherapy
FEC every three weeks for three cycles, followed by docetaxel, trastuzumab (T) and pertuzumab (P) every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 21 as adjuvant therapy post-surgery.
干预措施: Trastuzumab (Drug)
T+P Sequential Anthracycline-based chemotherapy
FEC every three weeks for three cycles, followed by docetaxel, trastuzumab (T) and pertuzumab (P) every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 21 as adjuvant therapy post-surgery.
干预措施: FEC (Drug)
T+P Sequential Anthracycline-based chemotherapy
FEC every three weeks for three cycles, followed by docetaxel, trastuzumab (T) and pertuzumab (P) every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 21 as adjuvant therapy post-surgery.
干预措施: Docetaxel (Drug)
T+P Concomitant Non-Anthracycline chemotherapy
Trastuzumab, carboplatin, docetaxel (TCH) and pertuzumab (P) every three weeks, for six cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
干预措施: Pertuzumab (Drug)
T+P Concomitant Non-Anthracycline chemotherapy
Trastuzumab, carboplatin, docetaxel (TCH) and pertuzumab (P) every three weeks, for six cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
干预措施: TCH (Drug)
结局指标
主要结局
Safety: Percentage of Participants With Symptomatic Cardiac Events as Assessed by the Investigator
时间窗: From baseline up to approximately 3.5 years
Left ventricular systolic dysfunction (LVSD) as assessed by the Investigator, including Grade 3, 4 or 5 symptomatic LVSD with symptomatic cardiac events.
Safety: Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Decline During Pre-operative (Neoadjuvant) Period
时间窗: From baseline up to approximately 18 weeks
Percentage of participants with LVEF measures decline of ≥ 10% from baseline and to a value of \<50% during the pre-operative (neoadjuvant) period.
次要结局
- Efficacy: Percentage of Participants With Complete Pathological Response (pCR)(At surgery, after 18 weeks (6 cycles) of treatment)
- Efficacy: Clinical Response Rate(During each 3-week cycle of 6 total cycles: up to 18 weeks)
- Efficacy: Time to Clinical Response(Up to 18 weeks)
- Efficacy: Percentage of Participants Achieving Breast Conserving Surgery(At approximately 18 weeks)
- Efficacy: Percentage of Participants Without an Overall Survival (OS) Event(From baseline to end of study up to 5 years)
- Efficacy: Percentage of Participants Without a Disease-Free Survival (DFS) Event(From baseline to end of study up to 5 years)
- Efficacy: Percentage of Participants Without a Progression-Free Survival (PFS) Event(From baseline to end of study up to 5 years)
- Safety: Percentage of Participants With Cardiac Symptoms Associated With Symptomatic Left Ventricular Systolic Dysfunction (LVSD)(From Baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years))
- Safety: Percentage of Participants With Asymptomatic Left Ventricular Ejection Fraction (LVEF) Events(From baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years))
- Safety: Maximum Decrease in Left Ventricular Ejection Fraction (LVEF) Measures(From baseline up to approximately 3.5 years)