A Randomized Phase III, Double-blind, Placebo-controlled Multicenter Trial of Daily Everolimus in Combination With Trastuzumab and Vinorelbine, in Pretreated Women With HER2/Neu Over-expressing Locally Advanced or Metastatic Breast Cancer.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 569
- 试验地点
- 44
- 主要终点
- Progressive-free Survival (PFS) Per Investigator Assessment
研究概览
简要总结
This phase III, double-blind, placebo-controlled multinational study will assess the combination everolimus, vinorelbine, and trastuzumab compared to the combination vinorelbine and trastuzumab with respect to progressive-free survival and over survival in HER2/neu positive women with locally advanced or metastatic breast cancer who are resistant to trastuzumab and have been pre-treated with a taxane.
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
- Double (Participant, Investigator)
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
- •Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
- •HER2+ status defined as IHC 3+ staining or in situ hybridization positive
- •Patients with resistance to trastuzumab
- •Prior taxane therapy
- •Patients with an ECOG performance status of 0 - 2
- •Patients with measurable disease as per RECIST criteria
- •Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study;
- •Patients must meet laboratory criteria defined in the study within 21 days prior to randomization
排除标准
- •Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer
- •More than three prior chemotherapy lines for advanced disease.
- •Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed >8 weeks prior to randomization
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
- •Peripheral neuropathy ≥ grade 2 at randomization
- •Active cardiac disease
- •History of cardiac dysfunction
- •Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
- •Known hypersensitivity to any study medication
- •Breastfeeding or pregnant
研究组 & 干预措施
Everolimus + vinorelbine + trastuzumab
Oral everolimus (5 mg/day) + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)
干预措施: everolimus (Drug)
Everolimus + vinorelbine + trastuzumab
Oral everolimus (5 mg/day) + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)
干预措施: vinorelbine (Drug)
Everolimus + vinorelbine + trastuzumab
Oral everolimus (5 mg/day) + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)
干预措施: trastuzumab (Drug)
placebo + vinorelbine + trastuzumab
Oral daily matching placebo + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only
干预措施: Placebo (Drug)
placebo + vinorelbine + trastuzumab
Oral daily matching placebo + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only
干预措施: vinorelbine (Drug)
placebo + vinorelbine + trastuzumab
Oral daily matching placebo + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only
干预措施: trastuzumab (Drug)
结局指标
主要结局
Progressive-free Survival (PFS) Per Investigator Assessment
时间窗: Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
PFS was defined as the time from the date of randomization to the date of first radiologically documented tumor progression or death from any cause, whichever occurs first. PFS primary analysis performed when 415 events were reached. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
次要结局
- Vinorelbine Blood Concentrations by Leading Dose and Time Point(Cycle 2, Day 1)
- PRO: Time to Deterioration in Global Health Status/QoL Domain Score of the European Organization for the Research and Treatment of Cancer (EORTC)-Core Quality of Life Questionnaire (QLQ-C30) (by at Least 10%)(Baseline, until disease progression or death up to about 41 months)
- Median Time to Deterioration of the ECOG Performance Status Score(baseline, until disease progression or death up to about 41 months)
- Overall Survival (OS)(Every 3 months until death up to 41 months)
- Overall Response Rate (ORR)(Every 6 weeks until disease progression or death which ever occurred first up to about 41 months)
- Clinical Benefit Rate (CBR)(Every 6 weeks until disease progression or death which ever occurred first up to about 41 months)
- Trastuzumab Blood Concentrations by Leading Dose and Time Point(Cycle 3, Day 1)
- Everolimus Blood Concentrations by Leading Dose and Time Point(Cycle 2, Day 1)