A Phase I Study of Pharmacokinetics and Safety of Trastuzumab Emtansine in Chinese Patients With Logically Advanced Inoperable or Metastatic HER2-Positive Breast Cancer Who Have Received Prior Trastuzumab Based Therapy

Hoffmann-La Roche1 个研究点分布在 1 个国家目标入组 11 人开始时间: 2017年6月20日最近更新: 2018年11月23日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Hoffmann-La Roche
入组人数: 11
试验地点: 1
主要终点: Maximum Serum Concentration (Cmax) Immediately After Dosing of Trastuzumab Emtansine, Total Trastuzumab, N2'-Deacetyl-N2'-(3-Mercapto-1-Oxopropyl)-Maytansine (DM1), Non-reducible Thioether Linkage (MCC)-DM1 and Lys-MCC-DM1

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is an open-label Phase I study of single-agent trastuzumab emtansine administered by intravenous (IV) infusion. The study will characterize the pharmacokinetics of trastuzumab emtansine and its relevant analytes and the safety of trastuzumab emtansine in Chinese participants with human epidermal growth factor receptor 2 (HER2)-positive locally advanced/metastatic breast cancer (LA/MBC).

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

•Prospective centrally-assessed HER2-positive disease (i.e., immunohistochemistry [IHC] 3 + and/or gene amplified [HER2 to CEP 17 ratio ≥ 2] by in situ hybridization [ISH]) through use of archival paraffin-embedded tumor tissue. Both IHC and ISH assays will be performed; however, only one positive result from either method is required for eligibility
•Tumor tissue block or eight unstained freshly cut slides must be available for central laboratory HER2 testing. Archival tumor samples obtained from primary and/or metastatic sites are acceptable
•For participants with bilateral BC, HER2-positive status must be demonstrated in both locations or in a metastatic site
•Histologically or cytologically confirmed invasive breast cancer (BC): incurable, unresectable, LABC previously treated with multimodality therapy or metastatic breast cancer (MBC)
•Prior treatment for BC in the adjuvant, unresectable, locally advanced, or metastatic setting must include taxane, alone or in combination with another agent, and trastuzumab, alone or in combination with another agent in the adjuvant, unresectable, locally advanced, or metastatic setting
•Documented progression of incurable, unresectable LABC or MBC: Progression must occur during or after most recent treatment for LABC or MBC or within 6 months after completing adjuvant therapy
•Baseline disease that must be evaluable per Response Evaluation Criteria for Solid Tumors Version 1.1 (RECIST v1.1). Participants with CNS-only disease are excluded
•Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
•Left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA)

排除标准

•Prior treatment with trastuzumab emtansine, lapatinib, or capecitabine
•Last dose of prior chemotherapy or trastuzumab within 21 days before the first dose of study treatment
•Hormonal therapy within 7 days before the first dose of study treatment
•Treatment with any other anti-cancer therapy/investigational drug (not defined above) within 21 days prior to randomization, except hormone therapy, which can be given up to 7 days prior to randomization; recovery of treatment-related toxicity consistent with other eligibility criteria before the first dose of treatment
•Radiation therapy within 2 weeks before the first dose of study treatment, and with any related acute toxicity (Grade ≥1)
•Brain metastases that are untreated, symptomatic, progressive, or require therapy, such as radiation or surgery, within 28 days before the first dose of study treatment
•History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, synchronous or previously diagnosed HER2-positive BC, or cancers with a similar curative outcome as those mentioned above
•Peripheral neuropathy Grade ≥3 per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4.03
•History of exposure to the following cumulative doses of anthracyclines as specified below:
•Doxorubicin > 500 mg/m^2
•Epirubucin > 720 mg/m^2
•Mitoxantrone > 120 mg/m^2 If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 500 mg/m^2 doxorubicin.
•Cardiopulmonary dysfunction as defined by:
•Uncontrolled hypertension (persistent systolic blood pressure >150 millimeter of mercury (mmHg) and/or diastolic blood pressure >100 mmHg despite anti-hypertensive therapy)
•Unstable angina or serious cardiac arrhythmia not controlled by medication
•Baseline LVEF <50% by either ECHO or MUGA scan
•History of symptomatic congestive heart failure (Grade ≥3 per NCI CTCAE v4.03 or Class ≥II per New York Heart Association criteria)
•History of LVEF <40% or symptomatic CHF during prior trastuzumab treatment
•Myocardial infarction within 6 months before the first dose of study treatment
•Current dyspnea at rest because of complications of advanced malignancy or any medical need for continuous oxygen therapy

研究组 & 干预措施

Trastuzumab Emtansine

Experimental

Participants with HER2-positive LA/MBC who received prior trastuzumab and taxane therapy will receive trastuzumab emtansine.

干预措施: Trastuzumab Emtansine (Drug)

结局指标

主要结局

Maximum Serum Concentration (Cmax) Immediately After Dosing of Trastuzumab Emtansine, Total Trastuzumab, N2'-Deacetyl-N2'-(3-Mercapto-1-Oxopropyl)-Maytansine (DM1), Non-reducible Thioether Linkage (MCC)-DM1 and Lys-MCC-DM1