A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate Pertuzumab in Combination With Docetaxel and Trastuzumab as Neoadjuvant Therapy, and Pertuzumab in Combination With Trastuzumab as Adjuvant Therapy After Surgery and Chemotherapy in Patients With Early-Stage or Locally Advanced HER2-Positive Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 329
- 试验地点
- 23
- 主要终点
- Percentage of Participants With Total Pathologic Complete Response (tpCR) as Assessed by the Independent Review Committee (IRC)
研究概览
简要总结
This is an Asia-Pacific regional, randomized, double-blind, multicenter trial designed to evaluate treatment with trastuzumab + pertuzumab + docetaxel compared with trastuzumab + placebo + docetaxel in chemotherapy-naïve participants with early-stage or locally advanced HER2-positive breast cancer. The anticipated treatment duration is approximately 17 months.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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 confirmed invasive breast carcinoma with a primary tumor size of more than (>) 2 centimeters (cm) by standard local assessment technique
- •Breast cancer stage at presentation: early-stage (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0; T4, any N, M0)
- •HER2-positive breast cancer confirmed by a Sponsor-designated central laboratory and defined as 3+ score by immunohistochemistry in > 10 percent (%) of immunoreactive cells or HER2 gene amplification (ratio of HER2 gene signals to centromere 17 signals equal to or more than [>=] 2.0) by in situ hybridization
- •Known hormone receptor status (estrogen receptor and/or progesterone receptor)
- •Eastern Cooperative Oncology Group Performance Status equal to or less than (<=) 1
- •Baseline left ventricular ejection fracture >= 55% measured by echocardiography (preferred) or multiple gated acquisition scan
- •Negative serum pregnancy test
排除标准
- •Stage IV metastatic breast cancer
- •Inflammatory breast cancer
- •Previous anti-cancer therapy or radiotherapy for any malignancy
- •History of other malignancy within 5 years prior to screening, except for appropriately-treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
- •Concurrent anti-cancer treatment in another investigational trial, including hormone therapy, bisphosphonate therapy, or immunotherapy
- •Major surgical procedure unrelated to breast cancer within 4 weeks prior to randomization or from which the participant has not fully recovered
- •Serious cardiac illness or medical condition
- •Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
- •Any abnormalities in liver, kidney or hematologic function laboratory tests immediately prior to randomization
- •Sensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol
- •Pregnant or lactating
研究组 & 干预措施
Trastuzumab, Pertuzumab, and Chemotherapy
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC): trastuzumab and pertuzumab up to 1 year total.
干预措施: FEC Chemotherapy (Drug)
Trastuzumab, Pertuzumab, and Chemotherapy
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC): trastuzumab and pertuzumab up to 1 year total.
干预措施: Surgery (Procedure)
Trastuzumab, Pertuzumab, and Chemotherapy
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC): trastuzumab and pertuzumab up to 1 year total.
干预措施: Docetaxel (Drug)
Trastuzumab, Pertuzumab, and Chemotherapy
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC): trastuzumab and pertuzumab up to 1 year total.
干预措施: Pertuzumab (Drug)
Trastuzumab, Pertuzumab, and Chemotherapy
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC): trastuzumab and pertuzumab up to 1 year total.
干预措施: Trastuzumab (Drug)
Trastuzumab, Placebo, and Chemotherapy
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy: trastuzumab and placebo up to 1 year total.
干预措施: FEC Chemotherapy (Drug)
Trastuzumab, Placebo, and Chemotherapy
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy: trastuzumab and placebo up to 1 year total.
干预措施: Surgery (Procedure)
Trastuzumab, Placebo, and Chemotherapy
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy: trastuzumab and placebo up to 1 year total.
干预措施: Docetaxel (Drug)
Trastuzumab, Placebo, and Chemotherapy
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy: trastuzumab and placebo up to 1 year total.
干预措施: Placebo (Drug)
Trastuzumab, Placebo, and Chemotherapy
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy: trastuzumab and placebo up to 1 year total.
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Percentage of Participants With Total Pathologic Complete Response (tpCR) as Assessed by the Independent Review Committee (IRC)
时间窗: At surgery (Cycle 4 Days 22-35)
This tpCR was assessed by the IRC. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer \[AJCC\] staging system). The analysis was based on the ITT population with participants grouped by the treatment assigned at the time of randomization. Participants whose tpCR assessment was missing or invalid were counted as not achieving tpCR. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point.
次要结局
- Percentage of Participants With bpCR as Assessed by the Local Pathologist(At surgery (Cycle 4 Days 22-35))
- Percentage of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) During Cycles 1-4, According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1(At surgery (Cycle 4 Days 22-35))
- Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Event-Free Survival (EFS) at 1, 3, and 5 Years(From Baseline to EFS event or date last known to be alive and event-free at 1, 3, and 5 years)
- Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Disease-Free Survival (DFS) at 1, 3, and 5 Years(From surgery (Cycle 4: Days 22-35) to DFS event or date last known to be alive and event-free at 1, 3, and 5 years)
- Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival (OS) at 1, 3, and 5 Years(From Baseline to OS event or date last known to be alive at 1, 3, and 5 years)
- Percentage of Participants With tpCR as Assessed by the Local Pathologist(At surgery (Cycle 4 Days 22-35))
- Percentage of Participants With Breast Pathologic Complete Response (bpCR), Defined as ypT0/is According to the AJCC Staging System as Assessed by the IRC(At surgery (Cycle 4 Days 22-35))
- Percentage of Participants With an Objective Response (CR or PR) During Cycles 1-4, According to RECIST Version 1.1(At surgery (Cycle 4 Days 22-35))
- Percentage of Participants With at Least One Adverse Event During the Treatment-Free Follow-Up Period(From end of overall study treatment until disease progression or until 5 years after randomization of the last patient, whichever occurred first (up to 6 years))
- Maximum Change From Baseline in LVEF(Baseline; Day 1 of Cycles 2, 4, 5, 8, 11, and 20 (1 cycle = 21 days))
- Percentage of Participants With at Least One Adverse Event (AE) During the Neoadjuvant Treatment Period(Baseline up to end of Cycle 4 (1 cycle = 21 days))
- Percentage of Participants With at Least One AE During the Adjuvant Treatment Period(From Cycle 5 (1 cycle = 21 days) up to 42 days after the last dose in Cycle 20 Day 1 (approximately 1 year))
- Percentage of Participants Who Experienced a Secondary Cardiac Event(From Baseline until end of study (up to 6 years))
- Change From Baseline in LVEF Over Time(Baseline; Day 1 of Cycles 2, 4, 5, 8, 11, and 20 (1 cycle = 21 days))
- Percentage of Participants Who Experienced a Primary Cardiac Event(From Baseline until end of study (up to 6 years))