A Randomized, Multicenter, Phase ii Study of the Efficacy and Safety of Trastuzumab-MCC-DM1 vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 137
- 主要终点
- Progression-free Survival (PFS) by the Investigator Using Modified Response Evaluation Criteria In Solid Tumors (RECIST)
研究概览
简要总结
This was a Phase II, randomized, multicenter, international, 2-arm, open-label clinical trial designed to explore the efficacy and safety of trastuzumab emtansine (T-DM1) relative to the combination of trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive, unresectable, locally advanced breast cancer and/or metastatic breast cancer who have not received prior chemotherapy for metastatic disease.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease, and a candidate for chemotherapy.
- •Human epidermal growth factor receptor 2 (HER2)-positive.
- •No prior chemotherapy for their metastatic breast cancer (MBC).
- •Measurable disease.
- •Age ≥ 18 years.
- •For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception or 2 effective forms of non-hormonal contraception by the patient and/or partner. Contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the study.
排除标准
- •History of any chemotherapy for MBC.
- •An interval of < 6 months from the completion of cytotoxic chemotherapy in the neo-adjuvant or adjuvant setting until the time of metastatic diagnosis.
- •Trastuzumab ≤ 21 days prior to randomization.
- •Hormone therapy < 7 days prior to randomization.
- •Current peripheral neuropathy of Grade ≥
- •History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those previously mentioned.
- •Previous radiotherapy for the treatment of unresectable, locally advanced or metastatic breast cancer is not allowed if more than 25% of marrow-bearing bone has been irradiated or the last fraction of radiotherapy has been administered within approximately 3 weeks prior to randomization.
- •Brain metastases that are untreated, symptomatic, or require therapy to control symptoms or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to randomization.
- •History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin > 500 mg/m^2; epirubicin > 900 mg/m^2; mitoxantrone > 120mg/m^2 and idarubicin > 90 mg/m^
- •Current unstable angina.
- •History of symptomatic congestive heart failure, or ventricular arrhythmia requiring treatment.
- •History of myocardial infarction within 6 months prior to randomization.
- •Left ventricular ejection fraction (LVEF) below 50% within approximately 28 days prior to randomization.
- •History of decreased LVEF or symptomatic congestive heart failure (CHF) with previous adjuvant trastuzumab treatment.
- •Cardiac troponin I ≥ 0.2 ng/mL within 28 days of randomization.
- •Severe dyspnea at rest because of complications of advanced malignancy or requiring current continuous oxygen therapy.
- •Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures).
- •Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment.
- •Current pregnancy or lactation.
- •History of receiving any investigational treatment within approximately 28 days prior to randomization.
- •Current known infection with human immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C virus.
- •History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins, or docetaxel.
- •Known hypersensitivity to any of the study drugs, including the excipients, or any drugs formulated in polysorbate
- •Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
研究组 & 干预措施
Trastuzumab emtansine
Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) administered over 30-90 minutes every 3 weeks on Day 1 of each 21-day cycle.
干预措施: Trastuzumab emtansine [Kadcyla] (Drug)
Trastuzumab + docetaxel
Patients received a loading dose of trastuzumab 8 mg/kg IV + docetaxel 75 or 100 mg/m^2 IV on Day 1 of Cycle 1 followed by trastuzumab 6 mg/kg IV + docetaxel 75 or 100 mg/m^2 IV on Day 1 of all subsequent 21-day cycles.
干预措施: Trastuzumab (Drug)
Trastuzumab + docetaxel
Patients received a loading dose of trastuzumab 8 mg/kg IV + docetaxel 75 or 100 mg/m^2 IV on Day 1 of Cycle 1 followed by trastuzumab 6 mg/kg IV + docetaxel 75 or 100 mg/m^2 IV on Day 1 of all subsequent 21-day cycles.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Progression-free Survival (PFS) by the Investigator Using Modified Response Evaluation Criteria In Solid Tumors (RECIST)
时间窗: Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)
PFS was defined as the time from randomization (R) to first documented investigator-assessed radiographic or clinical disease progression (PD) or death due to any cause, whichever occurred first. For target lesions (TL), PD was defined as at least a 20% increase in the sum of the longest diameter (SLD) of TLs, taking as reference the SLD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Data for patients without PD or death were censored at the last date of tumor assessment prior to crossover (or, if no tumor assessment was performed after Baseline, at the R date +1 day). Data for patients who were lost to follow-up were censored at the last date of tumor assessment prior to crossover at which the patient was known to be progression free. Data for patients with no post-baseline tumor assessment were censored at the R date +1 day.
次要结局
- Overall Survival(Baseline through the data cut-off date of 31 Aug 2011 (up to 2 years, 11 months))
- Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)(Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months))
- Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)(Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months))
- Clinical Benefit (CB) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)(Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months))
- Time to Symptom Progression(Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months))
- Serum Concentrations (Area Under the Concentration-time Curve [AUC]) of Trastuzumab Emtansine and Total Trastuzumab(Baseline through Cycle 5 (up to 4 months))
- Plasma Concentration of Free Emtansine(Baseline through Cycle 5 (up to 4 months))