A Multicenter, Multinational Phase II Study to Assess the Clinical Safety and Feasibility of Trastuzumab Emtansine Sequentially With Anthracycline-based Chemotherapy, as Adjuvant or Neoadjuvant Therapy for Patients With Early Stage HER2-positive Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 153
- 主要终点
- Percentage of Participants With a Cardiac Event Within 12 Weeks After the Start of Trastuzumab Emtansine Treatment
研究概览
简要总结
This single-arm open-label study assessed the safety, feasibility, and efficacy of trastuzumab emtansine (T-DM1) after the completion of anthracycline-based adjuvant/neoadjuvant chemotherapy in patients with early HER2-positive breast cancer. Patients received T-DM1 3.6 mg/kg intravenously on Day 1 of each 3-week cycle, for up to 17 cycles.
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
- •Adult patients ≥ 18 years of age.
- •Locally advanced, inflammatory, or early stage, unilateral, and histologically confirmed invasive breast cancer documented at a local laboratory (patients with inflammatory breast cancer must be able to have a core needle biopsy).
- •Herceptin (HER)2-positive tumor, confirmed by central testing using immunohistochemistry (IHC) and in situ hybridization (ISH) methods.
- •Willingness to receive anthracycline-based chemotherapy or have received doxorubicin/cyclophosphamide (AC) OR 5-fluorouracil (FU)/epirubicin/ cyclophosphamide (FEC) in a similar dose and schedule as described in the protocol as part of neoadjuvant or adjuvant treatment.
- •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 should use condoms for the duration of the study. Specific country requirements will be followed.
- •Negative results of serum pregnancy test for premenopausal women of reproductive capacity and for women < 12 months after menopause.
- •Patients may enroll before or after AC/FEC chemotherapy has completed.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate hematologic, biochemistry, and cardiac assessments.
排除标准
- •Stage IV breast cancer or bilateral breast cancer.
- •Pregnant or breastfeeding women.
- •History of other malignancy within the previous 5 years, except contralateral breast cancer and ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS), appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with outcome similar to those mentioned above.
- •Radiation therapy, immunotherapy, or biotherapy within 5 years before study enrollment; non-cardiotoxic chemotherapy for malignancy treated > 5 years before study enrollment is allowed. Patients receiving AC/FEC in a similar fashion to the study treatment prescribed for adjuvant or neoadjuvant treatment of breast cancer will be allowed to enroll in the study after the completion of their AC/FEC. No other prior history of cardiotoxic chemotherapy is allowed.
- •Active cardiac history.
- •Current chronic daily treatment with oral corticosteroids or equivalent.
- •Patients with severe dyspnea at rest or requiring supplementary oxygen therapy.
- •Active, unresolved infections at screening.
- •Human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.
- •Major surgery within 4 weeks before enrollment that is unrelated to the breast cancer.
- •Patients for whom concomitant radiotherapy + T-DM1 may be contraindicated yet radiation therapy is planned.
- •Known hypersensitivity to any of the study drugs or derivatives, including murine proteins.
- •Grade ≥ 2 peripheral neuropathy at Baseline.
研究组 & 干预措施
Trastuzumab emtansine
Trastuzumab emtansine 3.6 mg/kg was administered intravenously on Day 1 of each 3-week treatment cycle up to a maximum of 17 cycles.
干预措施: Trastuzumab emtansine (Drug)
结局指标
主要结局
Percentage of Participants With a Cardiac Event Within 12 Weeks After the Start of Trastuzumab Emtansine Treatment
时间窗: Baseline to 12 weeks after the start of trastuzumab emtansine treatment
A cardiac event was defined as death from a cardiac cause or severe congestive failure (New York Heart Association \[NYHA\] Class III or IV) with a decrease in left ventricular ejection fraction (LVEF) of ≥ 10% from Baseline to an LVEF of \< 50%.
Adverse Events, LVEF Function, and Deaths
时间窗: From the start to the end of trastuzumab emtansine treatment (up to 51 weeks)
The following percentages of participants are reported: At least 1 adverse event while receiving T-DM1; at least 1 serious adverse event while receiving T-DM1; an adverse event leading to discontinuation, dose delay, or dose reduction of trastuzumab emtansine treatment; symptomatic cardiac dysfunction; and asymptomatic decline in left ventricular ejection fraction (LVEF). An asymptomatic LVEF decline was defined as a LVEF \< 50% and a maximum decrease ≥ 10% from Baseline. The percentage of participants who died is reported.
次要结局
- Percentage of Participants Who Experienced at Least 1 Adverse Event During Concurrent Hormonal Therapy With Trastuzumab Emtansine Treatment(From the start to the end of concurrent hormonal therapy (up to 51 weeks))
- Percentage of Participants Who Completed the Planned Duration of Trastuzumab Emtansine Treatment(From the start to the end of trastuzumab emtansine treatment (up to 51 weeks))
- Percentage of Participants Who Experienced at Least 1 Adverse Event During Concurrent Radiotherapy With Trastuzumab Emtansine Treatment(From the start to the end of concurrent radiotherapy (up to 51 weeks))
- Percentage of Participants Who Completed ≥ 95% of the Planned Radiotherapy Treatment With Concurrent Trastuzumab Emtansine Administration Without Significant (> 5 Days) Delay(From the start to the end of radiotherapy treatment (up to 51 weeks))
- Percentage of Participants With a Pathological Complete Response(Day of surgery)
- Disease-free Survival at Month 12(From the start of trastuzumab emtansine for adjuvant patients and from the date of surgery for neoadjuvant patients to 12 months later)