A Randomised, Multicenter, Open-label, Phase II Study Evaluating Pyrotinib Plus Trastuzumab, Pertuzumab and Nab-paclitaxel as Neoadjuvant Therapy in Early Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2 - Positive Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 216
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Total Pathologic Complete Response (tpCR)
研究概览
简要总结
This study aims to evaluate the efficacy and safety of pyrotinib in combination with trastuzumab, pertuzumab and nab-paclitaxel as neoadjuvant therapy in early stage or locally advanced HER2-positive breast cancer.
详细描述
The study evaluate the pathological complete response rate, event-free survival, disease-free survival, overall survival and safety of pyrotinib in combination with trastuzumab, pertuzumab and nab-paclitaxel as neoadjuvant therapy in early stage or locally advanced HER2-positive breast cancer. Patients will receive 4 cycles of pyrotinib in combination with trastuzumab, pertuzumab and nab-paclitaxel or 4 cycles of trastuzumab, pertuzumab and nab-paclitaxel as neoadjuvant therapy, then undergo surgery, then receive adjuvant chemotherapy and targeted therapy according to pathologic response and physician's choice.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •With signed consent
- •Histologically confirmed invasive breast carcinoma with a primary tumor size of no less than (≥) 2 centimeters (cm) by standard local assessment technique
- •Breast cancer stage at presentation: stage II-III
- •HER2-positive breast cancer defined as 3+ score by immunohistochemistry in > 10 percent (%) of immunoreactive cells or HER2 gene amplification 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 >= 50% measured by echocardiography
- •Willing to use highly effective form of nonhormonal contraception while on study and for 7 months after end of study treatment for female with fertility or male
- •Willing to obey the study protocol
排除标准
- •Stage IV disease
- •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, ,Stage I uterine cancer or thyroid papillary microcarcinoma
- •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
- •Not able to swallow the drug
- •Pregnant or lactating
- •Positive serum or urine pregnancy test or above mentioned tests cannot be achieved for women with fertility
研究组 & 干预措施
Pyrotinib, trastuzumab, pertuzmab and paclitaxel
Prior to surgery: pyrotinib, trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice, followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: Pyrotinib (Drug)
Pyrotinib, trastuzumab, pertuzmab and paclitaxel
Prior to surgery: pyrotinib, trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice, followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: Trastuzumab (Drug)
Pyrotinib, trastuzumab, pertuzmab and paclitaxel
Prior to surgery: pyrotinib, trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice, followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: Pertuzumab (Drug)
Pyrotinib, trastuzumab, pertuzmab and paclitaxel
Prior to surgery: pyrotinib, trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice, followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: Nab-paclitaxel (Drug)
Pyrotinib, trastuzumab, pertuzmab and paclitaxel
Prior to surgery: pyrotinib, trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice, followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: EC chemotherapy (Drug)
Pyrotinib, trastuzumab, pertuzmab and paclitaxel
Prior to surgery: pyrotinib, trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice, followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: Physician's choice (Drug)
Pyrotinib, trastuzumab, pertuzmab and paclitaxel
Prior to surgery: pyrotinib, trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice, followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: T-DM1 (Drug)
Pyrotinib, trastuzumab, pertuzmab and paclitaxel
Prior to surgery: pyrotinib, trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice, followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: Surgery (Procedure)
Trastuzumab, pertuzmab and paclitaxel
Prior to surgery: trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice; followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: Trastuzumab (Drug)
Trastuzumab, pertuzmab and paclitaxel
Prior to surgery: trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice; followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: Pertuzumab (Drug)
Trastuzumab, pertuzmab and paclitaxel
Prior to surgery: trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice; followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: Nab-paclitaxel (Drug)
Trastuzumab, pertuzmab and paclitaxel
Prior to surgery: trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice; followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: EC chemotherapy (Drug)
Trastuzumab, pertuzmab and paclitaxel
Prior to surgery: trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice; followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: Physician's choice (Drug)
Trastuzumab, pertuzmab and paclitaxel
Prior to surgery: trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice; followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: T-DM1 (Drug)
Trastuzumab, pertuzmab and paclitaxel
Prior to surgery: trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).
After surgery：
- if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
- if tpCR: chemotherapy 0-4 cycles according to physician's choice; followed with pertuzumab and trastuzumab up to 1 year total.
干预措施: Surgery (Procedure)
结局指标
主要结局
Percentage of Participants With Total Pathologic Complete Response (tpCR)
时间窗: After completion of 4 cycles of neoadjuvant therapy. The duration of one treatment cycle is 21 days
tpCR is 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 duration of one treatment cycle is 21 days.
次要结局
- Clinical response(Cycle 1-4. The duration of one treatment cycle is 21 days.)
- Percentage of Participants With Breast Pathologic Complete Response (bpCR)(After completion of 4 cycles of neoadjuvant therapy The duration of one treatment cycle is 21 days. at the time of surgery)
- Event-free survival (EFS)(From Baseline to EFS event or date last known to be alive and event-free (up to 5 years))
- Disease-free survival (DFS)(From surgery to DFS event or date last known to be alive and event-free (up to 5 years))
- Overall survival (OS)(From Baseline to OS event or date last known to be alive (up to 5 years))
研究者
Kunwei Shen
Professor
Shanghai Jiao Tong University School of Medicine