Phase I Study of Pemetrexed and Sorafenib in Advanced Malignancy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Recommended phase 2 doses for the combination of pemetrexed disodium with sorafenib tosylate
研究概览
简要总结
This phase I trial studies the side effects and best dose of giving pemetrexed disodium and sorafenib tosylate together in treating patients with advanced solid tumors. Pemetrexed disodium and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of solid tumors by blocking blood flow to the tumor. Giving pemetrexed disodium together with sorafenib tosylate may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine doses for the combination of pemetrexed (pemetrexed disodium) with sorafenib (sorafenib tosylate) appropriate for Phase II study.
SECONDARY OBJECTIVES:
I. To evaluate the safety, tolerance, and toxicity of the combination of pemetrexed and sorafenib.
II. To observe antitumor effects of the combination.
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
- •Advanced solid tumor malignancy for which there is no potentially curative treatment; there is no limit to the number of prior lines of therapy
- •Performance status Eastern Cooperative Oncology Group (ECOG) equal or less than 1
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 x upper institutional limit (ULN)
- •Total bilirubin =< 1.5 ULN
- •Creatinine clearance (CrCl) >= 45 mL/min as measured by the standard Cockcroft-Gault equation
- •International normalized ratio (INR) =< 1.5 (if not due to anticoagulants)
- •White blood cell count (WBC) >= 3,000 cells/mm3
- •Absolute neutrophil count (ANC) >= 1,500 cells/mm3
- •Platelets >= 100,000 cells/mm3
- •Hemoglobin (Hgb) >= 8.5 g/dL
- •Prior toxicities are allowed as long as they are stable and would not interfere with study drug toxicity assessment
- •Measurable or evaluable disease by Response Evaluation Criteria In Solid Tumors (RECIST) (v 1.1)
- •Ability to understand and the willingness to sign a written informed consent document; a signed informed consent must be obtained prior to any study specific procedures
- •Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of treatment; women of childbearing potential and men must agree to use a medically accepted form of birth control for the duration of study participation; men must agree to use a medically accepted form of birth control for 2 months following completion of study treatment
排除标准
- •Any investigational agent within 4 weeks of first dose of study treatment
- •Unwillingness or inability to take folic acid, vitamin B12, or dexamethasone
- •Known or presumed intolerance of pemetrexed or sorafenib; unable to swallow medication; suspected malabsorption
- •Active illicit substance or alcohol abuse
- •Contraindication to antiangiogenic agents, including:
- •Pulmonary hemorrhage/bleeding event >= Grade 2 within 4 weeks or less prior to the first dose of study drug
- •Any other hemorrhage/bleeding event >= Grade 3 within 4 weeks or less prior to the first dose of study drug
- •Serious non-healing wound, ulcer, or bone fracture
- •Thrombolic or embolic events such as a myocardial infarction, cerebrovascular accident including transient ischemic attacks within the past 6 months
- •Major cardiac dysfunction, such as uncontrolled angina, congestive heart failure with New York Heart Association (NYHA) class III or higher, ventricular arrhythmias requiring anti-arrhythmic therapy
- •Systolic blood pressure > 160 mmHg or diastolic pressure > 100 mmHg despite optimal medical management
- •Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5 day period
- •Serious uncontrolled infection > Common Terminology Criteria for Adverse Events (CTCAE) (v 4) grade 2
- •Peripheral motor or sensory neuropathy>CTCAE (v4) grade 2
- •Uncontrolled metastatic brain disease
- •Serum B12 or folate levels below the institution's lower limit of normal. Patients may begin B12/folic acid supplementation and can be reconsidered for study once levels meet the eligibility requirements
- •Administration of non-steroidal anti-inflammatory drugs (NSAIDs) within 5 days prior to pemetrexed dosing (note: if a candidate routinely takes NSAIDs prior to enrollment, consider transition to alternate non-NSAID for duration of study treatment, if possible).
- •Other condition(s) that in the opinion of the investigator might compromise the objectives of the study
研究组 & 干预措施
Treatment (enzyme inhibitor therapy, antiangiogenesis)
Patients receive pemetrexed disodium IV on day 1 every 2 weeks and sorafenib tosylate PO BID for 4 weeks on days 1-5. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: sorafenib tosylate (Drug)
Treatment (enzyme inhibitor therapy, antiangiogenesis)
Patients receive pemetrexed disodium IV on day 1 every 2 weeks and sorafenib tosylate PO BID for 4 weeks on days 1-5. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: pemetrexed disodium (Drug)
Treatment (enzyme inhibitor therapy, antiangiogenesis)
Patients receive pemetrexed disodium IV on day 1 every 2 weeks and sorafenib tosylate PO BID for 4 weeks on days 1-5. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (enzyme inhibitor therapy, antiangiogenesis)
Patients receive pemetrexed disodium IV on day 1 every 2 weeks and sorafenib tosylate PO BID for 4 weeks on days 1-5. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: biopsy (Procedure)
结局指标
主要结局
Recommended phase 2 doses for the combination of pemetrexed disodium with sorafenib tosylate
时间窗: At least 4 weeks
Maximum doses of pemetrexed and sorafenib, which, when administered in combination are determined to be tolerable and will be tested in a Phase 2 trial for efficacy.
次要结局
- Number of subjects in whom study treatment produces antitumor effects of the combination(Up to 4 years)
- Number of biopsy specimens that successfully stain for Beclin1(Baseline up to 4 weeks)
- Number of biopsy specimens that can be analyzed for PDGFRb expression(Baseline up to 4 weeks)
- Analysis of pTEN expression in biopsy specimens(Baseline up to 4 weeks)