An Exploratory Phase II, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of Pertuzumab and Herceptin (Trastuzumab) in Patients With HER2-Positive Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 95
- 主要终点
- Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or Stable Disease (SD) According to RECIST Version 1.0 During Dual-Agent Treatment
研究概览
简要总结
This study will evaluate the efficacy and safety of Perjeta (pertuzumab) in combination with Herceptin (trastuzumab) in participants with metastatic breast cancer who have progressed on trastuzumab-based therapy (Cohorts 1 and 2), and will make a preliminary assessment of the efficacy and safety of single-agent pertuzumab (Cohort 3). Objective response rate and clinical benefit will be assessed. Pertuzumab will be administered at an initial dose of 840 milligrams (mg) intravenously (IV) on Day 1, followed by 420 mg IV every 3 weeks. Trastuzumab will be administered at the same schedule the participant was following before entry into the study. An additional cohort of participants at certain centers will receive pertuzumab monotherapy at an initial dose of 840 mg IV on Day 1, followed by 420 mg IV every 3 weeks. These participants may have trastuzumab added to the regimen in the event of progression during single-agent pertuzumab treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Females greater than or equal to (≥) 18 years of age, with histologically-confirmed HER2-positive breast cancer
- •Metastatic breast cancer, with progression on trastuzumab-based therapy as last treatment for metastatic disease
- •Less than or equal to (≤) 3 chemotherapy regimens prior to study entry
- •Last trastuzumab dose ≤9 weeks before study entry for participants receiving pertuzumab + trastuzumab, and ≥4 weeks for participants receiving pertuzumab monotherapy
- •Left ventricular ejection fraction ≥55% at study entry
排除标准
- •Previous treatment with an anti-cancer vaccine or any targeted therapy other than trastuzumab
- •Brain metastases
- •History of any cardiac adverse event related to trastuzumab therapy
- •Any other malignancy in the last 5 years, except for basal cell cancer or cancer in situ of the cervix
研究组 & 干预措施
Pertuzumab + Trastuzumab (Cohorts 1 and 2)
Females with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer will receive dual-agent treatment with pertuzumab and trastuzumab. Trastuzumab will be administered IV as 2 milligrams per kilogram (mg/kg) once weekly, or as 6 mg/kg every 3 weeks, beginning on Day 1 of Cycle 1. Pertuzumab will be administered IV at a loading dose of 840 mg followed by a standard dose of 420 mg every 3 weeks, beginning on Day 2 of Cycle 1. Thereafter, both medications will be administered on Day 1 of each 3-week cycle. Treatment will continue for a minimum of 8 cycles and may be extended until disease progression, intolerable toxicity, or death.
干预措施: Pertuzumab (Drug)
Pertuzumab + Trastuzumab (Cohorts 1 and 2)
Females with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer will receive dual-agent treatment with pertuzumab and trastuzumab. Trastuzumab will be administered IV as 2 milligrams per kilogram (mg/kg) once weekly, or as 6 mg/kg every 3 weeks, beginning on Day 1 of Cycle 1. Pertuzumab will be administered IV at a loading dose of 840 mg followed by a standard dose of 420 mg every 3 weeks, beginning on Day 2 of Cycle 1. Thereafter, both medications will be administered on Day 1 of each 3-week cycle. Treatment will continue for a minimum of 8 cycles and may be extended until disease progression, intolerable toxicity, or death.
干预措施: Trastuzumab (Drug)
Pertuzumab +/- Trastuzumab (Cohort 3)
Females with HER2-positive metastatic breast cancer will receive single-agent treatment with pertuzumab. Pertuzumab will be administered IV at a loading dose of 840 mg followed by a standard dose of 420 mg every 3 weeks, administered on Day 1 of each 3-week cycle. Participants with documented disease progression may have trastuzumab added to the regimen, per the dosing schedule described for Cohorts 1 and 2, to receive dual-agent treatment until disease progression, intolerable toxicity, or death.
干预措施: Pertuzumab (Drug)
Pertuzumab +/- Trastuzumab (Cohort 3)
Females with HER2-positive metastatic breast cancer will receive single-agent treatment with pertuzumab. Pertuzumab will be administered IV at a loading dose of 840 mg followed by a standard dose of 420 mg every 3 weeks, administered on Day 1 of each 3-week cycle. Participants with documented disease progression may have trastuzumab added to the regimen, per the dosing schedule described for Cohorts 1 and 2, to receive dual-agent treatment until disease progression, intolerable toxicity, or death.
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or Stable Disease (SD) According to RECIST Version 1.0 During Dual-Agent Treatment
时间窗: Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Tumor response was assessed using RECIST version 1.0 to determine the clinical benefit response (CBR) rate, or the percentage of participants with either confirmed CR or PR, or SD lasting at least 6 months. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The CBR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.
Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 During Dual-Agent Treatment
时间窗: Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Tumor response was assessed using RECIST version 1.0 to determine the objective response (OR) rate, or the percentage of participants with either confirmed CR or PR. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter compared to Baseline. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The OR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.
次要结局
- Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR or PR According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab(Up to approximately 7.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression))
- Cohorts 1 and 2: Duration of Response According to RECIST Version 1.0(Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression))
- Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or SD According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab(Up to approximately 7.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression))
- Cohorts 1 and 2: Time to Objective Response According to RECIST Version 1.0(Up to approximately 21 months (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression; final analysis using February 2008 cutoff date))
- Cohorts 1 and 2: Percentage of Participants With Disease Progression According to RECIST Version 1.0(Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression))
- Cohorts 1 and 2: Time to Progression (TTP) According to RECIST Version 1.0(Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression))
- Cohorts 1 and 2: Progression-Free Survival (PFS) According to RECIST Version 1.0(Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression))
- Cohorts 1 and 2: Percentage of Participants Who Died(Up to approximately 4.5 years (during treatment; then every 4 months until death, withdrawn consent, loss to follow-up, or 3 years after last dose; final analysis using November 2010 cutoff date))
- Cohorts 1 and 2: Overall Survival (OS)(Up to approximately 4.5 years (during treatment; then every 4 months until death, withdrawn consent, loss to follow-up, or 3 years after last dose; final analysis using November 2010 cutoff date))