A Randomized Phase III, Double-Blind, Placebo-Controlled Multicenter Trial of Everolimus in Combination With Trastuzumab and Paclitaxel, as First Line Therapy in Women With HER2 Positive Locally Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 719
- 试验地点
- 27
- 主要终点
- Progression-free Survival (PFS) Per Investigators' Assessment Based on Local Radiology Review - Full Population
研究概览
简要总结
The purpose of this Phase III study was to confirm the value of adding everolimus to weekly paclitaxel and trastuzumab as treatment of HER2-overexpressing metastatic breast cancer.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Adult Women (≥ 18 years old).
- •Histologically or cytologically confirmed invasive breast carcinoma with local recurrence or radiological evidence of metastatic disease.
- •Must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease.
- •HER2+ patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
- •Prior trastuzumab and/or chemotherapy (taxanes included) as neo-adjuvant or adjuvant treatment is allowed but should be discontinued > 12 months prior to randomization.
- •Prior treatment for breast cancer with endocrine therapy (adjuvant or metastatic settings) is allowed but should be discontinued at randomization. Patients treated with bisphosphonates at entry or who start bisphosphonates during study may continue this therapy during protocol treatment.
- •Documentation of negative pregnancy test.
- •Organ functions at time of inclusion.
排除标准
- •Prior mTOR inhibitors for the treatment of cancer.
- •Other anticancer therapy for locally advanced or metastatic breast cancer except for prior hormonal therapy.
- •Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites, etc).
- •Radiotherapy to ≥ 25% of the bone marrow within 4 weeks prior to randomization
- •History of central nervous system metastasis.
- •Impairment of gastrointestinal (GI) function or GI disease or active ulceration of the upper gastrointestinal tract.
- •Serious peripheral neuropathy.
- •Cardiac disease or dysfunction.
- •Uncontrolled hypertension.
- •Pregnant,
研究组 & 干预措施
Everolimus + Paclitaxel + Trastuzumab
Everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22
干预措施: Everolimus (Drug)
Everolimus + Paclitaxel + Trastuzumab
Everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22
干预措施: Trastuzumab (Drug)
Everolimus + Paclitaxel + Trastuzumab
Everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22
干预措施: Paclitaxel (Drug)
Placebo + Paclitaxel + Trastuzumab
Placebo of everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22
干预措施: Placebo (Drug)
Placebo + Paclitaxel + Trastuzumab
Placebo of everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22
干预措施: Trastuzumab (Drug)
Placebo + Paclitaxel + Trastuzumab
Placebo of everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression-free Survival (PFS) Per Investigators' Assessment Based on Local Radiology Review - Full Population
时间窗: date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to about 56 months
PFS is defined as the time from the date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first. This was assessed in the full patient population.
Progression-free Survival (PFS) Per Investigators' Assessment Based on Local Radiology Review - (Hormone Receptor (HR)-Negative Population
时间窗: date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to about 56 months
PFS is defined as the time from the date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first. This was assessed in the HR-negative patient population.
次要结局
- Overall Survival (OS) - Full Population(up to about 76 months)
- Overall Response Rate (ORR) - Full Population(up to about 23 months)
- Time to Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Score - Full Population(up to about 56 months)
- Overall Response Rate (ORR) - HR-negative Population(up to about 23 months)
- Clinical Benefit Rate (CBR) Equal to or Greater Than 24 Weeks - Full Population(up to about 23 months)
- Clinical Benefit Rate (CBR) Equal to or Greater Than 24 Weeks - HR-negative Population(up to about 23 months)
- Time to Overall Response Based on Investigator - Full Population(up to about 23 months)
- Overall Response (OR) - Full Population(up to about 23 months)
- Paclitaxel Plasma Concentrations(Cycle 2/Day 15 (Pre-infusion and end of infusion))
- Overall Survival (OS) - HR-negative Population(up to about 76 months)
- Time to Overall Response Based on Investigator - HR-negative Population(up to about 23 months)
- Overall Response (OR) - HR-negative Population(up to about 23 months)
- Everolimus Blood Level Concentrations at Steady States for Everolimus(predose, 2 hours post-dose at Cycle 2/Day 1, Cycle 2/Day 15, Cycle 2/ Day 22)
- Trastuzumab Serum Concentrations(Cycle 4/Day 1 (Pre-infusion and end of infusion))
- Time to Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Score - HR-negative Population(up to about 56 months)