Phase I Study of the Combination of Vemurafenib With Carboplatin and Paclitaxel in Patients With Advanced Malignancy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Vemurafenib with Carboplatin and Paclitaxel
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of vemurafenib that can be given in combination with carboplatin and paclitaxel patients with advanced cancer. The safety of the study drug combination will also be studied.
Vemurafenib is designed to block a protein (called mutated BRAF) that is only found in moles (spots) of the skin and certain types of cancer cells. This drug may slow the growth of or kill these cells.
Carboplatin is designed to slow the growth of cancer cells by stopping them from making new DNA (the genetic material of cells).
Paclitaxel is designed to slow the growth of cancer cells by stopping them from dividing into new cells.
详细描述
Study Groups:
If you are found to be eligible and decide to take part, you will be assigned to a study group based on when you join this study. Up to 8 groups of 3-6 participants will be enrolled in this study.
The dose of vemurafenib and the doses of carboplatin and paclitaxel you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of vemurafenib, carboplatin, and paclitaxel. Each new group will receive a higher dose level of the study drug combination than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination is found. After that, 10 additional participants will be enrolled.
Study Drug Administration:
Each study cycle is 3 weeks.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must be age >/= 12 years.
- •Patient must have histologically or cytologically confirmed diagnosis of advanced solid tumor or lymphoma harboring a BRAF mutation, for which no standard therapy is available, is resistant/refractory to standard therapy, has relapsed after standard therapy, or has no standard therapy that improves survival by at least three months.
- •Patient with QTc interval must be less than 500 msec.
- •Patient must have completed any prior cytotoxic chemotherapy or radiation therapy at least 21 days prior to starting the study drug(s), except selective RAF inhibitors (vemurafenib, dabrafenib or LGX818). There is no washout period for prior selective RAF inhibitors. Patients must be at least 5 half-lives or 3 weeks, whichever is shorter, from their previous targeted or biologic therapy. Local palliative radiation therapy that is not delivered to all target lesions is allowed immediately before or during treatment.
- •Patients must have evaluable disease for response.
- •Patient must have an ECOG performance status of 0 to
- •Patient must have adequate liver and renal function as documented by the following laboratory test results within 14 days prior to starting therapy: total bilirubin less than or equal to 2 x upper limit of normal (ULN) (exceptions may apply to benign non-malignant indirect hyperbilirubinemia such as Gilbert syndrome); AST (SGOT) and ALT (SGPT) less than or equal to 2.5 X ULN or less than or equal to 5 X ULN if liver metastasis is present; serum creatinine less than or equal to 2 X ULN
- •Patient must have adequate bone marrow function as documented by the following laboratory test results within 14 days prior to starting therapy: platelets greater than 75,000/mm^3;absolute neutrophil count (ANC) greater than 1000/mm^3; hemoglobin greater than 8.0 g/dL
- •Patient (man or woman) must agree to practice effective contraception during the entire study period, unless documentation of infertility exists, and for at least 4 weeks after the last dose of the study drug(s).
- •Patient must be willing and able to sign the informed consent form.
排除标准
- •Patients with clinically significant illnesses which could compromise participation in the study, including, but not limited to: active or uncontrolled infection; or unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled cardiac arrhythmia.
- •Patients with an inability to swallow tablets or capsules
- •Patients with leptomeningeal disease;
- •Patients who are pregnant or breastfeeding
研究组 & 干预措施
Vemurafenib + Carboplatin + Paclitaxel
All 3 study drugs will start on day 1 of cycle 1. Cycle defined as 3 weeks. On day 1, paclitaxel and carboplatin will be administered first, and the vemurafenib administration will start in the evening that day.
Starting dose of Paclitaxel: 100 mg/m2 by vein every 3 weeks.
Starting dose of Carboplatin: AUC 5 by vein every 3 weeks.
Starting dose of Vemurafenib: 480 mg by mouth mouth in the evening on Day 1 of Cycle 1, then twice a day starting on Day 2 for a 3 week cycle.
干预措施: Vemurafenib (Drug)
Vemurafenib + Carboplatin + Paclitaxel
All 3 study drugs will start on day 1 of cycle 1. Cycle defined as 3 weeks. On day 1, paclitaxel and carboplatin will be administered first, and the vemurafenib administration will start in the evening that day.
Starting dose of Paclitaxel: 100 mg/m2 by vein every 3 weeks.
Starting dose of Carboplatin: AUC 5 by vein every 3 weeks.
Starting dose of Vemurafenib: 480 mg by mouth mouth in the evening on Day 1 of Cycle 1, then twice a day starting on Day 2 for a 3 week cycle.
干预措施: Carboplatin (Drug)
Vemurafenib + Carboplatin + Paclitaxel
All 3 study drugs will start on day 1 of cycle 1. Cycle defined as 3 weeks. On day 1, paclitaxel and carboplatin will be administered first, and the vemurafenib administration will start in the evening that day.
Starting dose of Paclitaxel: 100 mg/m2 by vein every 3 weeks.
Starting dose of Carboplatin: AUC 5 by vein every 3 weeks.
Starting dose of Vemurafenib: 480 mg by mouth mouth in the evening on Day 1 of Cycle 1, then twice a day starting on Day 2 for a 3 week cycle.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Vemurafenib with Carboplatin and Paclitaxel
时间窗: 6 weeks
Maximum tolerated dose (MTD) defined as highest dose studied in which the incidence of the dose limiting toxicity (DLT) is \< 33%. If at any time more than or equal to one third of participants at a dose level experience DLT, that dose is considered to be above the MTD.
次要结局
- Overall Response Rate(6 weeks)