A Phase 1 Trial of CCI-779 in Combination With EKB-569, an EGFR Inhibitor, in Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients
研究概览
简要总结
This phase I trial is studying the side effects, best way to give, and best dose of CCI-779 and EKB-569 in treating patients with advanced solid tumors. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. EKB-569 may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Giving CCI-779 together with EKB-569 may kill more tumor cells.
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose of the combination of CCI-779 and EKB-569 in patients with advanced solid tumors.
II. Determine the toxicity of this regimen in these patients. III. Determine the response rate in patients treated with this regimen.
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 3 treatment groups.
Group I: Patients receive oral EKB-569 on days 1-28 and oral CCI-779 on days 1-7 and 15-21.
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
- •Histologically confirmed unresectable solid tumor for which there is no known standard therapy that is potentially curative or capable of extending life expectancy
- •No CNS metastases
- •Performance status - ECOG 0-2
- •At least 12 weeks
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Hemoglobin ≥ 10 g/dL
- •Bilirubin normal
- •AST ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver involvement)
- •Creatinine ≤ 1.5 times ULN
- •No New York Heart Association class III or IV heart disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 3 months after study participation
- •Fasting cholesterol < 350 mg/dL
- •Fasting triglycerides < 400 mg/dL
- •No uncontrolled infection
- •No seizure disorder
- •More than 4 weeks since prior immunotherapy
- •More than 4 weeks since prior biologic therapy
- •No concurrent immunotherapy
- •No concurrent prophylactic colony-stimulating factor therapy
- •More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
- •No other concurrent chemotherapy
- •No concurrent oral contraceptives
- •More than 4 weeks since prior radiotherapy
- •No prior radiotherapy to > 30% of bone marrow
- •No concurrent radiotherapy
- •More than 7 days since prior CYP3A4 inducers
- •No prior mTOR-targeting agents
- •No prior epidermal growth factor receptor-targeting agents
- •No concurrent antiretroviral therapy that induces or inhibits CYP3A4 for HIV-positive patients
- •No other concurrent investigational agents
- •No concurrent warfarin
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral EKB-569 on days 1-28 and oral CCI-779 on days 1-7 and 15-21.
干预措施: pelitinib (Drug)
Arm I
Patients receive oral EKB-569 on days 1-28 and oral CCI-779 on days 1-7 and 15-21.
干预措施: temsirolimus (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients
时间窗: Up to 28 days
Number and severity of all adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
时间窗: Up to 30 days after last dose of study treatment
Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
次要结局
- Best response according to the Response Evaluation Criteria in Solid Tumors (RECIST)(Time from the start of the treatment until disease progression/recurrence, assessed up to 3 years)
- Time until any treatment related toxicity(Up to 3 years)
- Time until treatment related grade 3+ toxicity(Up to 3 years)
- Time until hematologic nadirs (white blood cells [WBC], absolute neutrophil count [ANC], platelets)(Up to 3 years)
- Time to progression(Up to 3 years)
- Time to treatment failure(Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 years)