A Randomized, Two-Arm, Open-Label, Multicenter Phase II Trial Assessing the Efficacy and Safety of Pertuzumab Given in Combination With Trastuzumab Plus an Aromatase Inhibitor in First Line Patients With HER2-Positive and Hormone Receptor-Positive Advanced (Metastatic or Locally Advanced) Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 258
- 试验地点
- 82
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This randomized, open-label, two-arm, multi-center, Phase II study will evaluate the efficacy and safety of pertuzumab in combination with trastuzumab plus an aromatase inhibitor (AI) in first-line participants with HER2-positive and hormone receptor-positive advanced breast cancer. Participants will be randomized to one of two treatment arms; Arm A (pertuzumab in combination with trastuzumab plus an AI) or Arm B (trastuzumab plus an AI). Participants may also receive induction chemotherapy (a taxane, either docetaxel or paclitaxel) at the investigator's discretion in combination with the assigned treatment arm. The anticipated time on study treatment is until disease progression, unacceptable toxicity, withdrawal of consent, or death whichever occurs first.
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
- •Participants with HER2-positive and hormone receptor-positive advanced metastatic or locally advanced breast cancer
- •Post-menopausal status over 1 year
- •HER2-positive as assessed by local laboratory on primary or metastatic tumor
- •Hormone-receptor positive defined as estrogen receptor-positive and/or progesterone receptor-positive
- •At least one measurable lesion and/or non-measurable disease evaluable according to Response Evaluation Criteria In Solid Tumors Version 1.1
排除标准
- •Previous systemic non-hormonal anticancer therapy in the metastatic or locally advanced breast cancer setting
- •Previous treatment with anti-HER2 agents for breast cancer, except trastuzumab and/or lapatinib in the neoadjuvant or adjuvant setting
- •Disease progression while receiving adjuvant trastuzumab and/or lapatinib treatment
- •History of persistent Grade 2 or higher hematological toxicity according to National Cancer Institute-Common Toxicity Criteria Version 4.0
- •Disease-free interval from completion of adjuvant/neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months
- •Other malignancies within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma
- •Clinical or radiographic evidence of central nervous system metastases or significant cardiovascular disease
研究组 & 干预措施
Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy
Participants will receive pertuzumab in combination with trastuzumab plus aromatase inhibitor (AI) until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Participants may also receive induction chemotherapy (docetaxel every 3 weeks or paclitaxel weekly) up to the first 18-24 weeks of the treatment period at the investigator's discretion.
干预措施: Pertuzumab (Drug)
Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy
Participants will receive pertuzumab in combination with trastuzumab plus aromatase inhibitor (AI) until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Participants may also receive induction chemotherapy (docetaxel every 3 weeks or paclitaxel weekly) up to the first 18-24 weeks of the treatment period at the investigator's discretion.
干预措施: Trastuzumab (Drug)
Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy
Participants will receive pertuzumab in combination with trastuzumab plus aromatase inhibitor (AI) until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Participants may also receive induction chemotherapy (docetaxel every 3 weeks or paclitaxel weekly) up to the first 18-24 weeks of the treatment period at the investigator's discretion.
干预措施: Aromatase Inhibitor (Drug)
Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy
Participants will receive pertuzumab in combination with trastuzumab plus aromatase inhibitor (AI) until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Participants may also receive induction chemotherapy (docetaxel every 3 weeks or paclitaxel weekly) up to the first 18-24 weeks of the treatment period at the investigator's discretion.
干预措施: Induction Chemotherapy (Drug)
Arm B: Trastuzumab + AI +/- Chemotherapy
Participants will receive trastuzumab plus aromatase inhibitor (AI) until predefined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Participants may also receive induction chemotherapy (docetaxel every 3 weeks or paclitaxel weekly) up to the first 18-24 weeks of the treatment period at the investigator's discretion.
干预措施: Trastuzumab (Drug)
Arm B: Trastuzumab + AI +/- Chemotherapy
Participants will receive trastuzumab plus aromatase inhibitor (AI) until predefined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Participants may also receive induction chemotherapy (docetaxel every 3 weeks or paclitaxel weekly) up to the first 18-24 weeks of the treatment period at the investigator's discretion.
干预措施: Aromatase Inhibitor (Drug)
Arm B: Trastuzumab + AI +/- Chemotherapy
Participants will receive trastuzumab plus aromatase inhibitor (AI) until predefined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Participants may also receive induction chemotherapy (docetaxel every 3 weeks or paclitaxel weekly) up to the first 18-24 weeks of the treatment period at the investigator's discretion.
干预措施: Induction Chemotherapy (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B
Progression-free survival (PFS) was defined as the time from randomization until the first radiographically documented progression of disease or death from any cause, whichever occurred first (either during study treatment or during follow-up). Progression of disease was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 and is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum of target lesion diameters must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progression). Participants with no PFS events were censored at the time of the last evaluable tumor assessment. The primary analysis of PFS was planned to be performed when a total of 165 PFS events had occurred, and the final analysis after at least 60 months follow-up.
次要结局
- Overall Survival (OS)(Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B)
- Change From Baseline in Health-Related Quality of Life as Determined by European Quality of Life 5-Dimension (EQ-5D) Visual Analog Scale (VAS) Scores(Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days))
- Overview of the Number of Participants With Adverse Events, Severity Determined According to NCI-CTCAE Version 4.03(From Baseline until the end of post-treatment follow-up (up to 89 months))
- Time to Response (TTR)(Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B)
- Number of Participants Who Died Over the Course of the Study by Reported Cause of Death and Time of Death Relative to First or Last Dose of Study Treatment(From Baseline until the end of post-treatment follow-up (up to 89 months))
- Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study(Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days))
- Duration of Response (DOR)(Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B)
- Overall Response Rate (ORR)(Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B)
- Clinical Benefit Rate (CBR)(Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B)