A Multicenter Randomized Phase III Study to Compare the Combination Trastuzumab and Capecitabine, With or Without Pertuzumab, in Patients With HER2-Positive Metastatic Breast Cancer That Have Progressed After One Line of Trastuzumab-Based Therapy in the Metastatic Setting (PHEREXA)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 452
- 试验地点
- 190
- 主要终点
- Progression Free Survival (Independent Assessment)
研究概览
简要总结
This randomized, two-arm study evaluated the efficacy and safety of a combination of trastuzumab and capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The study population consisted of female patients, whose disease had progressed during or following previous trastuzumab therapy for metastatic disease. All patients in Arm A and Arm B received trastuzumab (8 mg/kg iv as loading dose and then 6 mg/kg iv every 3 weeks thereafter) and capecitabine oral twice daily for 14 days every 3 weeks (1250 mg/m2 twice daily in Arm A and 1000 mg/m2 twice daily in Arm B). In addition, patients in Arm B received pertuzumab (840 mg iv as loading dose and then 420 mg iv thereafter) every 3 weeks. Study treatment continued until disease progression or unacceptable toxicity.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adult female patients >/=18 years of age
- •Metastatic HER2 positive breast cancer
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Disease progression during or following trastuzumab-based therapy for 1st line metastatic breast cancer (trastuzumab must have been part of the last prior treatment regimen)
- •Prior treatment with taxane-containing regimen
- •Left ventricular ejection fraction (LVEF) >/=50 percent
- •For women of childbearing potential agreement to use highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by patient and/or partner. Contraception must continue for duration of study treatment and for at least 6 months after last dose of study drug treatment
排除标准
- •Prior treatment with pertuzumab or capecitabine
- •Concurrent treatment with other experimental drug
- •Concurrent immunotherapy or anticancer hormonal therapy
- •Serious concurrent disease (e.g. active infection, uncontrolled hypertension, cardiovascular disease)
- •Central nervous system (CNS) metastases, which are not well controlled
- •History of exposure to anthracycline cumulative dose equivalent to 360mg/m2
- •History of congestive heart failure of any New York Heart Association criteria, or serious cardiac arrhythmia requiring treatment
- •History of myocardial infarction within 6 months prior to randomization
- •History of LVEF decline to below 50% during or after prior trastuzumab therapy or other cardiac toxicity during previous trastuzumab treatment that necessitated discontinuation of trastuzumab
- •History of another cancer which could affect compliance or result interpretation
- •Inadequate organ function
- •Pregnant or breastfeeding women
- •life expectancy < 12 weeks
研究组 & 干预措施
A: Capecitabine + Trastuzumab
干预措施: Trastuzumab (Drug)
A: Capecitabine + Trastuzumab
干预措施: Capecitabine (Drug)
B: Capecitabine + Trastuzumab + Pertuzumab
干预措施: Capecitabine (Drug)
B: Capecitabine + Trastuzumab + Pertuzumab
干预措施: Pertuzumab (Drug)
B: Capecitabine + Trastuzumab + Pertuzumab
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Progression Free Survival (Independent Assessment)
时间窗: Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).
Progression Free Survival (PFS) was defined as the time from randomization to first documented disease progression (PD), as determined by an Independent Review Facility (IRF) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. IRF review of tumor assessment ceased after the primary PFS analysis. The primary endpoint was analyzed after approximately 337 IRF-assessed PFS events were observed.
次要结局
- Overall Survival (OS) Rate Based on a 2-year Truncated Analysis(From randomization until death from any cause (up to 2 years))
- Overall Survival (OS)(From randomization until death from any cause (up to 7.5 years).)
- Investigator Assessment Progression-Free Survival (PFS)(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 7.5 years).)
- Time to Progression (TTP) Based Upon Independent Review Facility (IRF) Assessment(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).)
- Time to Treatment Failure (TTF) Based Upon Independent Review Facility (IRF) Assessment(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).)
- Overall Objective Response Rate (ORR)(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).)
- Clinical Benefit Rate (CBR)(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).)
- Duration of Objective Response(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).)