An Open-label, Multicentre, Phase IIIb Study With Intravenous Administration of Pertuzumab, Subcutaneous Trastuzumab, and a Taxane in Patients With HER2-positive Metastatic Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 13
- 主要终点
- Percentage of Participants With Adverse Events (AEs) and Serious AEs
研究概览
简要总结
This open-label, multicenter, Phase IIIb study will assess the safety, tolerability and efficacy of a combination therapy of intravenous (IV) pertuzumab (Perjeta), trastuzumab (Herceptin) SC, and taxane chemotherapy (docetaxel, paclitaxel or nab-paclitaxel) as first-line therapy in participants with HER2-positive metastatic breast cancer (mBC). All participants will be treated with 3-week cycles of pertuzumab IV (840 milligrams [mg] first dose; subsequent doses of 420 mg) and trastuzumab SC (600 milligrams [mg]). The taxane treatment regimen will be determined by the investigator. Participants will continue therapy until disease progression, unacceptable toxicity, or the participant withdraws consent, whichever occurs first.
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
- •HER2-positive disease, with an immunohistochemistry score of 3+ or in situ hybridization (ISH)-positive on primary tumor or metastatic site
- •Histologically or cytologically confirmed adenocarcinoma of the breast with metastatic disease with at least one measurable lesion and/or non-measurable disease according to RECIST Version 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2 for participants who will receive paclitaxel or nab-paclitaxel chemotherapy and ECOG 0-1 for participants who will receive docetaxel chemotherapy
- •LVEF of greater than or equal to (>=) 50 percent (%) measured by ECHO or MUGA scan before the first doses of pertuzumab and trastuzumab
- •Previous use of either adjuvant or neoadjuvant anti-HER2 therapy is allowed
- •Hormonal therapy will be allowed as per institutional guidelines. Hormonal therapy cannot be administered in combination with taxane therapy
排除标准
- •Previous systemic non-hormonal anticancer therapy for treatment of mBC
- •History of other cancers. Participants with curatively treated carcinoma in situ of the cervix or basal cell carcinoma and participants with other curatively-treated cancers who have been disease-free for at least 5 years are eligible. Participants with previous ductal carcinoma in situ (DCIS) of the breast are also eligible for the study
- •Pregnant or breastfeeding women. Positive serum pregnancy test in women of childbearing potential, premenopausal or less than 12 months of amenorrhea post-menopause, within 7 days before the first dose of pertuzumab and trastuzumab
- •Current peripheral neuropathy of Grade 3 or greater (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4.0)
- •Radiographic evidence of central nervous system (CNS) metastases as assessed by computed tomography (CT) or magnetic resonance imaging (MRI), unless they have been treated and have been stable for at least 3 months and do not require ongoing corticosteroid treatment
- •Participants with other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
- •Inadequate organ function
- •Serious cardiac illness or medical conditions that would preclude the use of trastuzumab
- •Participants with severe dyspnea at rest or requiring supplementary oxygen therapy
- •Concurrent enrollment in another clinical study using an investigational anti-cancer treatment, within 28 days before the first doses of trastuzumab and pertuzumab
研究组 & 干预措施
Trastuzumab SC, Pertuzumab, and Taxane
Participants will receive pertuzumab, trastuzumab and a taxane (docetaxel, paclitaxel or nab-paclitaxel) once every 3 weeks (21-day cycles). Choice of taxane will be at the discretion of the investigator and administered per routine clinical practices and local prescribing instructions.
干预措施: Docetaxel (Drug)
Trastuzumab SC, Pertuzumab, and Taxane
Participants will receive pertuzumab, trastuzumab and a taxane (docetaxel, paclitaxel or nab-paclitaxel) once every 3 weeks (21-day cycles). Choice of taxane will be at the discretion of the investigator and administered per routine clinical practices and local prescribing instructions.
干预措施: Nab-paclitaxel (Drug)
Trastuzumab SC, Pertuzumab, and Taxane
Participants will receive pertuzumab, trastuzumab and a taxane (docetaxel, paclitaxel or nab-paclitaxel) once every 3 weeks (21-day cycles). Choice of taxane will be at the discretion of the investigator and administered per routine clinical practices and local prescribing instructions.
干预措施: Paclitaxel (Drug)
Trastuzumab SC, Pertuzumab, and Taxane
Participants will receive pertuzumab, trastuzumab and a taxane (docetaxel, paclitaxel or nab-paclitaxel) once every 3 weeks (21-day cycles). Choice of taxane will be at the discretion of the investigator and administered per routine clinical practices and local prescribing instructions.
干预措施: Pertuzumab (Drug)
Trastuzumab SC, Pertuzumab, and Taxane
Participants will receive pertuzumab, trastuzumab and a taxane (docetaxel, paclitaxel or nab-paclitaxel) once every 3 weeks (21-day cycles). Choice of taxane will be at the discretion of the investigator and administered per routine clinical practices and local prescribing instructions.
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events (AEs) and Serious AEs
时间窗: Baseline up to 28 days after last study drug administration (up to 36 months)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Percentage of participants with AEs and SAEs was reported. AEs included both SAEs and non-SAEs. The 95% confidence interval (CI) was computed using Clopper-Pearson method.
Percentage of Participants With AEs by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Intensity Grades
时间窗: Baseline up to 28 days after last study drug administration (up to 36 months)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Intensity of AEs were graded according to NCI CTCAE version 4.0 on a 5-point scale: Grade 1=Mild, intervention not indicated; Grade 2=Moderate, local or noninvasive intervention indicated; Grade 3=Severe or medically significant but not immediately life-threatening; Grade 4= Life-threatening consequences, urgent intervention indicated; and Grade 5=Death related to AE. Percentage of participants with AEs by maximum severity grades was reported.
Percentage of Participants With AEs of Suspected Cardiac Origin, by New York Heart Association Classification (NYHA)
时间窗: Baseline up to 28 days after last study drug administration (up to 36 months)
NYHA functional classification includes: Class I (no limitation in physical activity; ordinary physical activity does not cause fatigue, breathlessness or palpitation), Class II (slight limitation of physical activity; ordinary physical activity results in fatigue, palpitation, breathlessness or angina pectoris), Class III (marked limitation of physical activity; less than ordinary activity will lead to symptomatically 'moderate' heart failure) and Class IV (inability to carry out any physical activity without discomfort; symptoms of congestive cardiac failure are present even at rest). Percentage of participants with AEs suspected to be of cardiac origin by maximum NYHA classification was reported.
Percentage of Participants With AEs Leading to Premature Discontinuation of Investigational Medicinal Products (IMPs)
时间窗: Baseline up to 28 days after last study drug administration (up to 36 months)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Percentage of participants with AEs leading to premature discontinuation of IMPs (pertuzumab and trastuzumab) was reported. AEs included both SAEs and non-SAEs. The 95% CI was computed using Clopper-Pearson method.
Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Below 50%
时间窗: Baseline up to 28 days after last study drug administration (up to 36 months)
LVEF was assessed using echocardiography (ECHO) or multiple-gated acquisition (MUGA) scans. Percentage of participants with LVEF below 50% at any time during the study was reported.
次要结局
- Percentage of Participants Who Died During Receiving Second-Line of Treatment(From start of second-line of treatment (any time from baseline up to 35 months) up to death due to any cause or study end (up to approximately 36 months))
- Percentage of Participants Who Died Due to Any Cause(Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months))
- Percentage of Participants With PD (Assessed According to RECIST Version 1.1) or Death Due to Any Cause(Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months))
- Progression-free Survival (PFS) Assessed According to RECIST Version 1.1(Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months))
- Number of Participants Receiving Second-Line Treatment by Treatment Type(Baseline up to approximately 35 months)
- Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1(Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months))
- Overall Survival (OS)(Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months))
- Event-free Survival (EFS) Assessed According to RECIST Version 1.1(Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months))
- OS During Second-Line of Treatment(From start of second-line of treatment (any time from baseline up to 35 months) up to death due to any cause or study end (up to approximately 36 months))