An Open-Label, Phase I, Dose-Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 4
- 主要终点
- Safety: Incidence of adverse events
研究概览
简要总结
This is an open-label, multicenter, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0994 in patients with locally advanced or metastatic solid tumors. Patients will be enrolled in one of two stages: a dose-escalation stage (Stage I) or the subsequent expansion stage (Stage II). Stage I will evaluate the safety, tolerability, and pharmacokinetics of increasing doses of GDC-0994 administered daily. Stage II will gather additional data on safety, tolerability, and pharmacokinetics of the recommended dose of GDC-0994 determined in Stage I.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Other
- 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
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Histologically or cytologically documented, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable
- •Evaluable disease or disease measurable per RECIST 1.1
- •Life expectancy >= 12 weeks
- •Adequate hematologic and end organ function
- •Consent to provide archival tissue
排除标准
- •History of prior significant toxicity from another MEK or ERK inhibitor requiring discontinuation of treatment
- •History of parathyroid disorder or history or malignancy-associated hypercalcemia requiring therapy in the past 6 months
- •Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis or neurosensory retinal detachment
- •History of glaucoma
- •Intraocular pressure > 21 mmHg as measured by tonometry
- •Predisposing factors to retinal vein occlusion, including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy
- •History of retinal vein occlusion (RVO), neurosensory retinal detachment, or neovascular macular degeneration
- •Allergy or hypersensitivity to components of the GDC-0994 formulation
- •Palliative radiotherapy within 2 weeks prior to first dose of study drug treatment in Cycle 1
- •Experimental therapy within 4 weeks prior to first dose of study drug treatment in Cycle 1
- •Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose of study drug treatment in Cycle 1, or anticipation of the need for major surgery during the course of study treatment
- •Prior anti-cancer therapy within 28 days or 5 times the half-life whichever is longer
- •Current severe, uncontrolled systemic disease
- •History of clinically significant cardiac dysfunction
- •Pregnancy, lactation, or breastfeeding
- •Active autoimmune disease
- •Inability or unwillingness to swallow pills
- •Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
- •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 warfarin or thrombolytic anticoagulants
- •Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment
研究组 & 干预措施
Stage I-Dose Escalation
干预措施: GDC-0994 (Drug)
Stage II-Cohort-Expansion
干预措施: GDC-0994 (Drug)
结局指标
主要结局
Safety: Incidence of adverse events
时间窗: Approximately 2 years
Maximum tolerated dose
时间窗: Approximately 2 years
Dose-limiting toxicities
时间窗: Approximately 2 years
Pharmacokinetics: Area under the concentration-time curve
时间窗: Approximately 2 years
Pharmacokinetics: Time to maximum plasma concentration
时间窗: Approximately 2 years
Pharmacokinetics: Apparent terminal elimination half-life
时间窗: Approximately 2 years
Pharmacokinetics: Maximum plasma concentrations
时间窗: Approximately 2 years
Pharmacokinetics: Minimum plasma concentrations
时间窗: Approximately 2 years
次要结局
- To assess the PD effects of GDC-0994, as measured by changes in molecular biomarkers in pre- and post-treatment tumor tissues\n(Approximately 2 years)
- Objective Response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(Approximately 2 years)
- Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(Approximately 2 years)
- Duration of response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(Approximately 2 years)