A Phase I/II Study of Paclitaxel, Carboplatin and YM155 (Survivin Suppressor) in Subjects With Solid Tumors (Phase I) and Advanced Non-Small Cell Lung Carcinoma (Phase II)
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
- Phase 1 Safe and Tolerable Phase 2 Dose.
研究概览
简要总结
Background:
- Carboplatin-paclitaxel is a commonly used chemotherapy combination for advanced non-small-cell lung carcinoma (NSCLC) and other solid tumors. In a randomized clinical trial, the combination of carboplatin, paclitaxel, and the additional chemotherapy drug bevacizumab had a better response rate and survival compared to carboplatin and paclitaxel alone. However, this trial treated only patients with a specific diagnosis and treatment risks. Further research is needed to determine whether this combination is useful for other diagnoses.
- YM155 is a drug that targets a type of chemical often found in cancer cells. It has been investigated in several phase I and phase II clinical trials, and it has been shown to be well tolerated and moderately effective in treating advanced NSCLC in patients who had not responded well to one or two standard treatments.
Objectives:
- To determine the efficacy of the combination of carboplatin, paclitaxel, and YM155 in the treatment of non-small-cell lung cancer.
Eligibility:
- Individuals 18 years of age and older who have been diagnosed with advanced non-small-cell lung carcinoma or other solid tumors for which standard therapy is not likely to be effective.
Design:
- Before the start of the study, participants will be screened with a medical history, blood tests, imaging scans of the affected areas, tumor biopsies, and other tests as directed by the study doctors.
- Participants will be treated for six 21-day cycles, or 18 weeks of treatment. Each cycle will include blood tests and imaging studies as required.
- On day 1 of each cycle, participants will receive an infusion of paclitaxel and carboplatin, followed by a 4-day infusion of YM155 (through a portable electronic infusion pump).
- Participants will have a computed tomography scan or other imaging every other cycle (approximately every 6 weeks) to determine whether the therapy is affecting the cancer site.
- After the sixth cycle, participants will return for follow-up visits at least every 3 months, and will be asked to remain in contact with the researchers to allow further study of the long-term effects of the treatment.
详细描述
Background:
- Treatment with platinum-based doublet chemotherapy results in a median survival of 7 to 10 months in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).
- Carboplatin-paclitaxel is a commonly used regimen in advanced NSCLC and other solid tumors. In a randomized clinical trial carboplatin, paclitaxel plus bevacizumab resulted in improved efficacy (response rate and survival) compared to carboplatin and paclitaxel alone but only patients with non-squamous histology and who were considered low risk of bleeding were treated. Improvement of survival was not confirmed in another randomized study with a different chemotherapy backbone.
- Novel treatment strategies need to be developed for advanced NSCLC.
- YM155 is a transcriptional inhibitor of survivin, an inhibitor of apoptosis protein. Pre-clinical activity of YM155 has been observed in several solid tumors, including NSCLC models and synergy was observed in combination with chemotherapeutic drugs, including carboplatin and paclitaxel.
- YM155 has been investigated in several phase I and phase II clinical trials and it has been shown to be well tolerated with the most common toxicities reported as being reversible and of grades 1 -2 in severity. In addition, as a monotherapy YM155 alone has shown modest antitumor activity in a phase II trial in advanced NSCLC in patients who had failed one or two prior chemotherapy lines.
Primary Objectives:
- In the Phase I portion of the study the primary objective will be to determine a safe and tolerable phase II dose of YM155 based upon dose limiting toxicities (DLTs) when YM155 is administered over 72 hours by continuous intravenous infusion (CIVI) every 3 weeks in combination with paclitaxel and carboplatin.
- In the Phase II portion of the study the primary objective will be to determine the objective response rate (ORR = partial response (PR)+ complete response (CR)) of YM155 in combination with carboplatin and paclitaxel in the first line treatment of patients with advanced NSCLC.
Secondary Objectives:
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
YM155 in Solid Tumors
Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m^2, dose level 2:5 mg/m^2 , dose level 3:6 mg/m^2, dose level 4:8 mg/m^2, dose level 5:10 mg/m^2 (MTD), dose level 6:12 mg/m^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days).
Phase II: 10 mg/m^2 (MTD)intravenous infusion over 72 hours every 21 days.
干预措施: YM155 (Drug)
YM155 in Solid Tumors
Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m^2, dose level 2:5 mg/m^2 , dose level 3:6 mg/m^2, dose level 4:8 mg/m^2, dose level 5:10 mg/m^2 (MTD), dose level 6:12 mg/m^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days).
Phase II: 10 mg/m^2 (MTD)intravenous infusion over 72 hours every 21 days.
干预措施: Carboplatin (Drug)
YM155 in Solid Tumors
Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m^2, dose level 2:5 mg/m^2 , dose level 3:6 mg/m^2, dose level 4:8 mg/m^2, dose level 5:10 mg/m^2 (MTD), dose level 6:12 mg/m^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days).
Phase II: 10 mg/m^2 (MTD)intravenous infusion over 72 hours every 21 days.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Phase 1 Safe and Tolerable Phase 2 Dose.
时间窗: 1 year
Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m\^2, dose level 2:5 mg/m\^2 , dose level 3:6 mg/m\^2, dose level 4:8 mg/m\^2, dose level 5:10 mg/m\^2 (MTD), dose level 6:12 mg/m\^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days). Phase 2 dose is based upon dose limiting toxicities experienced during cycle 1.
Phase 2 Objective Response Rate (Partial Response (PR) + Complete Response (CR)).
时间窗: up to 18 weeks
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Number of Participants With Adverse Events
时间窗: 31.5 months
Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
次要结局
未报告次要终点
研究者
Arun Rajan, M.D.
Principal investigator
National Institutes of Health Clinical Center (CC)