A Phase I Trial of Sirolimus and Cetuximab in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 165
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicities (DLT) of Combination Treatment with Sirolimus and Cetuximab
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of the combination of sirolimus and cetuximab that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.
详细描述
The Study Drugs:
Cetuximab is designed to prevent or slow down the growth of cancer cells by blocking protein on the surface of the cancer cell, called the epidermal growth factor receptor (EGFR).
Sirolimus is designed to block a protein called mTOR inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill the cancer cells.
Study Drug Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of cetuximab and sirolimus based on when you joined this study. Up to 9 dose levels of cetuximab and sirolimus will be tested. Three (3) to 9 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination of cetuximab and sirolimus is found.
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
- •Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
- •Patients must be >/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment providing radiation is not delivered to the only site of disease being treated under this protocol. For biologic/targeted agents patients must be >/= 5 half-lives or >/= 3 weeks form the last dose (whichever comes first).
- •Eastern Cooperative Oncology Group (ECOG) performance status </=
- •Patients must have normal organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/=50,000/mL; creatinine </= 3 X upper limit of normal (ULN); total bilirubin </= 2.0; ALT(SGPT) </= 5 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 8 X ULN; cholesterol </= 350 mg/dL; triglycerides </= 400 mg/dL.
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
- •Patients with colorectal cancer with Kirsten rat sarcoma (kRAS) mutations (mutational status must be available prior to entering the study)
- •Patients must be able to understand and be willing to sign a written informed consent document.
排除标准
- •Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
- •Pregnant or lactating women.
- •History of hypersensitivity to cetuximab, murine products, or any component of the formulation.
- •History of hypersensitivity to sirolimus.
- •History of hypersensitivity to any component of the formulation.
- •Patients with colorectal cancer with kRAS mutations. (mutational status must be available prior to entering the study)
- •Patients unwilling or unable to sign informed consent document.
研究组 & 干预措施
Sirolimus + Cetuximab
Sirolimus beginning dose 3 mg by mouth on Day 1, and 1 mg on Days 2 - 28 for a 28 day cycle. Cetuximab Beginning dose 100 mg/m^2 by vein over two hours on Day 1, and 65 mg/m^2 on Days 8, 15 and 22 for a 28 day cycle.
干预措施: Sirolimus (Drug)
Sirolimus + Cetuximab
Sirolimus beginning dose 3 mg by mouth on Day 1, and 1 mg on Days 2 - 28 for a 28 day cycle. Cetuximab Beginning dose 100 mg/m^2 by vein over two hours on Day 1, and 65 mg/m^2 on Days 8, 15 and 22 for a 28 day cycle.
干预措施: Cetuximab (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicities (DLT) of Combination Treatment with Sirolimus and Cetuximab
时间窗: 4 weeks
MTD defined by DLTs that occur in the first cycle (4 weeks). DLT defined as any clinically grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v3.0, expected and believed to be related to the study medications (except nausea and vomiting, electrolyte imbalances responsive to appropriate regimens or alopecia), any grade 4 hematologic toxicity lasting at least 3 weeks or longer (as defined by the NCI-CTC v3.0) or associated with bleeding and/or sepsis; any grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens, and any other grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 that is attributable to therapy.
次要结局
未报告次要终点