NCT00928330已完成1 期
A Phase Ib, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, and Activity of Trastuzumab and Trastuzumab-MCC-DM1 Administered Intravenously and GDC-0941 Administered Orally to Patients With HER2-Positive Metastatic Breast Cancer Who Have Progressed on Previous Trastuzumab-Based Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 57
- 主要终点
- Incidence, nature, and severity of adverse events
研究概览
简要总结
This multicenter, Phase Ib study is an open label, dose escalation, three-arm study evaluating the safety, tolerability, pharmacokinetics, and activity of oral (PO) GDC 0941 administered in combination with either intravenous (IV) infusion of T-DM1 or IV infusion of trastuzumab.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically documented locally advanced or metastatic breast cancer that has progressed on at least one trastuzumab-based regimen in the metastatic or locally advanced setting
- •HER2-positive disease documented by one of the following results using FDA-approved testing methods: FISH-positive, chromogenic in situ hybridization (CISH)-positive, or IHC 3 + by local laboratory assessment
- •Life expectancy >= 90 days
- •Agreement to use an effective form of contraception for the duration of the study
排除标准
- •History of Grade >= 3 hypersensitivity reaction to trastuzumab, or Grade >= 1 with the most recent trastuzumab infusion before study entry, or continued requirement for prolonged trastuzumab infusions to prevent hypersensitivity reactions
- •History of intolerance to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued
- •Prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy, hormonal therapy) within 2 weeks prior to Day 1
- •Prior investigational anti-cancer therapy within 4 weeks prior to Day 1
- •Grade >= 2 peripheral neuropathy
- •History of Grade >= 3 hyperglycemia (fasting)
- •History of Type 1 or Type 2 diabetes requiring daily medication
- •History of clinically significant cardiac or pulmonary dysfunction
- •History of malabsorption syndrome or other condition that would interfere with enteral absorption
- •Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with HIV, hepatitis B virus, or hepatitis C virus
- •Any condition requiring anticoagulants, such as warfarin, heparin, or thrombolytic agents
- •Any condition requiring > 2 grams of acetaminophen daily
- •Need for current chronic corticosteroid therapy
- •Pregnancy, lactation, or breast-feeding
- •Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
- •Major surgical procedure or significant traumatic injury within 28 days prior to Day 1, or anticipation of the need for major surgery during the course of study treatment
- •Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
- •Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
研究组 & 干预措施
A
Experimental
干预措施: GDC-0941 (Drug)
A
Experimental
干预措施: trastuzumab-MCC-DM1 (Drug)
B
Experimental
干预措施: GDC-0941 (Drug)
B
Experimental
干预措施: trastuzumab-MCC-DM1 (Drug)
C
Experimental
干预措施: GDC-0941 (Drug)
C
Experimental
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Incidence, nature, and severity of adverse events
时间窗: Through study completion or early study discontinuation
Changes in cardiac function
时间窗: Through study completion or early study discontinuation
Changes in vital signs, physical findings, and clinical laboratory results during and following administration of study drugs that result in dose modification, dose delay, or discontinuation of T-DM1 and/or GDC 0941
时间窗: Through study completion or early study discontinuation
次要结局
- PK parameters of T-DM1 and GDC-0941 (total exposure, maximum serum concentration, and minimum concentration)(Through study completion or early study discontinuation)
- Progression-free survival (PFS)(From study treatment initiation to the first occurrence of disease progression or death on study)
- Objective response based on investigator assessment(Confirmed response >/= 4 weeks after initial documentation of response)
- Duration of response(Time from initial complete or partial response to the time of disease progression or death on study)
研究者
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