Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 462
- 试验地点
- 52
- 主要终点
- Event free survival at three years
研究概览
简要总结
This is a multicenter, single arm, phase II study evaluating the efficacy of image-guided de-escalating neoadjuvant treatment with paclitaxel, Herceptin® (trastuzumab), carboplatin, and pertuzumab (PTC-Ptz) in stage II-Ill HER2-positive breast cancer.
详细描述
High pathological complete response (pCR)-rates are seen using different neoadjuvant chemotherapy schedules with trastuzumab and pertuzumab in HER2-positive stage II - III breast cancer patients. Total pCR rates in breast and axilla have been described as high as 64%, and with an even higher rate of >80% in patients with HER2-positive and hormone receptor (HR) negative tumors. PCR is associated with better long-term outcomes in patients with HER2-positive breast cancer. Three year progression-free survival ranges between 85-90%. Neoadjuvant treatment of HER2-positive breast cancer typically consists of six to nine cycles of treatment. Longer duration of treatment is associated with higher pCR-rates but gives more toxicity. Pathological complete responses are sometimes seen after only 10-12 days of neoadjuvant treatment. It is therefore important to investigate which patients can safely be treated with less than six cycles of chemotherapy and who requires more than six cycles for maximum activity.
The radiologic response of a breast tumor after neoadjuvant therapy is predictive of the pathologic response, although the accuracy differs between breast cancer subtypes. It is hypothesized that patients with an early complete radiologic response may not benefit from additional chemotherapy and can be referred for early surgery. Patients who have not achieved pCR after early surgery despite radiologic complete response (rCR) are candidates for further adjuvant chemotherapy to complete the initially planned number of treatment cycles and maintain maximum treatment activity. Imaged guided de-escalation in which the number of treatment cycles is determined by the radiologic response could thus reduce toxicity in neoadjuvant treatment while maintaining activity.
This study will evaluate the efficacy of image-guided de-escalation of neoadjuvant chemotherapy in patients with HER2-positive breast cancer.
To maintain efficacy, patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1. Patients who achieve early pCR will continue treatment with Herceptin® and pertuzumab to complete one full year of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 confirmed primairy infiltrating breast cancer.
- •Stage II or Ill disease.
- •Overexpression and/or amplification of HER2 in an invasive component of the core biopsy.
- •ECOG Group performance status
- •LVEF >50% measured by echocardiography, MRI or MUGA
- •Known HR-status ( in percentages)
排除标准
- •Previous radiation therapy of chemotherapy
- •Pregnancy or breastfeeding
- •Evidence of distant metastases
- •Evidence of bilateral infiltrating breast cancer
- •Concurrent anti-cancer treatment or another investigational drug
研究组 & 干预措施
PTC-Pz
- Paclitaxel 80mg/m2 administered intravenously on day 1 and day 8
- Herceptin® 6mg/kg administered intravenously on day 1 (loading dose 8mg/kg) or Herceptin® administered subcutaneously 600mg on day 1
- Carboplatin AUC 6mg•ml/min administered intravenously on day 1
- Pertuzumab 420mg administered intravenously on day 1 (loading dose 840mg)
- Treatment cycles are repeated on day 22
Patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1.
干预措施: PTC-Pz (Drug)
结局指标
主要结局
Event free survival at three years
时间窗: 3 years
Number of patients without progression of disease recurrence, second primary or death
次要结局
- Overall survival at three years(3 years)
- Pathologic complete response in breast and axilla(an average of 6 months)
- Radiologic complete response(an average of 6 months)
- Number of neoadjuvant chemotherapy cycles administered(an average of 1 year)
- Number of radical and non-radical resections(an average of 6 months)
- Incidence and severity of adverse events(an average of 1 year)
- Incidence of symptomatic LVSD (heart failure),(an average of 1 year)
- Grade ≥3 laboratory test abnormalities(an average of 1 year)
- Incidence and severity of cardiotoxicity and neuropathy(an average of 1 year)
- Incidence of number of tumor positive Vacuum Assisted Core Biopsy(an average 6 months)