A Phase I Study of Ixabepilone in Combination With Carboplatin in Patients With Non-small Cell Lung Cancer as First-line Treatment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose of Carboplatin in Combination With Ixabepilone, 32 mg/m^2
研究概览
简要总结
The purpose of this study is to determine the maximum tolerated dose, dose-limiting toxicity, and recommended Phase II dose of ixabepilone in combination with carboplatin in patients with non-small cell lung cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥20 years
- •Histologic or cytologic diagnosis of advanced non-small cell lung cancer (NSCLC)
- •Advanced NSCLC, defined as stage IIIB (without indications for radiotherapy), stage IV, or recurrent
- •No prior chemotherapy-containing regimens for the treatment of NSCLC
- •Eastern Cooperative Oncology Group performance status of 0-1
- •Life expectancy of at least 12 weeks
- •Accessible for treatment and follow up; patients who could be hospitalized for first 15 days of Cycle 1
- •Adequate recovery from previous systemic therapy (at least 3 weeks for surgery or radiation therapy)
排除标准
- •Women of childbearing potential (WOCBP) unwilling or unable to use an acceptable method to avoid pregnancy for study period and for up to 4 weeks after last dose of study drug
- •Women pregnant or breast feeding
- •Women with a positive pregnancy test result on enrollment or prior to study drug administration
- •Sexually active fertile men not using effective birth control for the entire study period and for up to 3 months after the last dose of study drug if their partners are WOCBP
- •Patients with symptomatic or requiring treatment for brain metastases and/or leptomeningeal metastases
- •Prior radiation must not have included ≥30% of major bone-marrow-containing areas (pelvis, lumbar spine)
- •Common Terminology Criteria (CTC) Grade 2 or greater neuropathy
- •Psychiatric or other disorders rendering the patient incapable of complying with protocol requirements
- •Any concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix (Patients with a history of malignancy but without evidence of disease for 5 years are eligible)
- •Serious uncontrolled medical disorder or active systemic infection that would impair the ability of the subject to receive protocol therapy.
- •Myocardial infarction, unstable angina, or unstable congestive heart failure within 6 months
- •Known history of infection with human immunodeficiency virus
- •Inadequate bone marrow function
- •Inadequate hepatic function
- •Inadequate renal function
- •Known prior severe hypersensitivity reaction (CTC Grade 2 or greater) to agents containing Cremophor®EL
- •Known severe hypersensitivity reaction to agents containing carboplatin and other platinum
- •Prior treatment with an epothilone and/or with platinum
- •History of high-dose chemotherapy with bone marrow transplant or peripheral blood stem cell support within 2 years
- •On treatment with strong Cytochrome P450 3A4 inhibitor
- •Current imprisonment
- •Compulsorily detention for treatment of psychiatric or physical illness
研究组 & 干预措施
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/min/mL
干预措施: Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/min/mL (Drug)
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/min/mL
干预措施: Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/min/mL (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose of Carboplatin in Combination With Ixabepilone, 32 mg/m^2
时间窗: Days 1 through 21 (Cycle 1)
The MTD was defined as the highest dose evaluated for which less than one sixth of patients experience a DLT in Cycle 1. The recommended phase 2 dose is the MTD defined in Cycle 1, with consideration given to chronic cumulative toxicity occurring at later cycles.
Number of Participants With Dose-limiting Toxicity (DLT)
时间窗: Days 1 through 21 (Cycle 1)
DLT is defined as any of the following: Common Terminology Criteria (CTC), Version 3, Grade(Gr) 4 neutropenia (absolute neutrophil count \<500 cells/mm\^3) for at least 5 days or febrile neutropenia; Gr 4 thrombocytopenia (\<25,000 cells/mm\^3 or bleeding needing platelet transfusion); Gr 3 or 4 nausea, vomiting, or diarrhea, despite medical intervention; any other drug-related Gr 3 or 4 nonhematologic toxicity, except Gr 3 injection site reaction, fatigue/asthenia, transient arthralgia/myalgia, or transient electrolytes abnormal. Gr 1=Mild; Gr 2=Moderate; Gr 3=Severe; Gr 4=Life-threatening.
次要结局
- Number of Participants With Grade 3 or Greater Treatment-related AEs(Days 1 through 21 (Cycle 1))
- Number of Participants With Abnormalities in Urine Testing Results by Worst CTC Grade(At screening and Days 8 and 15 of Cycle 1 (21 days))
- Time of Maximum Observed Plasma Concentration of Ixabepilone(Days 1 to 8 of Cycle 1 (21 days))
- Number of Participants With Abnormalities in Hematology Laboratory Values by Worst CTC Grade(At screening and Days 8 and 15 of Cycle 1 (21 days))
- Number of Participants With Abnormalities in Serum Chemistry Laboratory Values by Worst CTC Grade(At screening and Days 8 and 15 of Cycle 1 (21 days))
- Maximum Observed Plasma Concentration of Ixabepilone(Days 1 to 8 of Cycle 1 (21 days))
- Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinite Time of Ixabepilone(Days 1 to 8 of Cycle 1 (21 days))
- Number of Participants With Death as Outcome, Treatment-related Serious Adverse Events (SAEs), SAEs, Adverse Events (AEs), and Treatment-related AEs Leading to Discontinuation(Days 1 through 21 (Cycle 1))
- Number of Participants With Abnormalities in Blood Pressure and Heart Rate(At screening and Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (Study day 22))
- Number of Participants With Abnormalities in Weight and Eastern Cooperative Oncology Group (ECOG) Performance Status(At screening of Cycle 1 (21 days) and Day 1 of Cycle 2 (Study day 22))
- Number of Participants at Each Response Evaluation Criteria in Solid Tumors (RECIST) Assessment(Days 1 through 21 (Cycle 1))
- Volume of Distribution at Steady State of Ixabepilone(Days 1 to 8 of Cycle 1 (21 days))
- Total Body Clearance of Ixabepilone(Days 1 to 8 of Cycle 1 (21 days))