Phase II Randomized Study of Vorinostat or Placebo in Combination With Carboplatin and Paclitaxel for Patients With Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 13
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving carboplatin and paclitaxel together is more effective with or without vorinostat in treating non-small cell lung cancer.
详细描述
PRIMARY OBJECTIVES:
I. To compare progression-free survival associated with the combination of carboplatin, paclitaxel and vorinostat versus carboplatin, paclitaxel and placebo for patients with previously untreated, advanced NSCLC.
SECONDARY OBJECTIVES:
I. To determine the response rate, time to treatment failure, and overall survival for the two regimens.
II. To assess the safety profile of the regimen of vorinostat, carboplatin and paclitaxel for patients with advanced NSCLC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 must have histologically confirmed non-small cell lung cancer
- •No prior chemotherapy for advanced or metastatic disease
- •ECOG performance status 0 or 1
- •Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
- •Life expectancy of greater than 12 weeks
- •Leukocytes >= 3,000/mcL
- •Absolute neutrophil count >= 1,500/mcL
- •Platelets >= 100,000/mcL
- •Total bilirubin within normal institutional limits
- •AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal
- •Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Patients who have had chemotherapy or radiotherapy in a metastatic setting
- •Patients may not be receiving any other investigational agents
- •Patients with untreated brain metastases should be excluded from this clinical trial; however, patients who have stable brain disease (should be off corticosteroids) at least 3 weeks after completion of appropriate therapy are eligible
- •Patients who have received any prior HDAC inhibitor (except valproic acid for seizure control provided that the valproic acid has been stopped at least 30 days before beginning therapy on this protocol) are excluded from this study
- •Peripheral neuropathy of severity greater than grade 1
- •Known history of allergic reactions to paclitaxel
- •Prior therapy with paclitaxel
- •Inability to take oral medications on a continuous basis; patients unable to swallow the vorinostat capsules whole are ineligible (the capsules cannot be crushed or broken)
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with vorinostat; women of childbearing potential must use an appropriate double barrier method of birth control (such as female use of a diaphragm, intrauterine device [IUD], sponge and spermicide, in addition to the male use of a condom) or a prescribed birth control implant or practice abstinence; both double barrier contraception and implants must be used for at least one week prior to the start of the research study and continue for at least two weeks following the last study visit; please note that birth control pills should not be used while on this study as they may have a negative interaction with the experimental drug in this study
- •HIV-positive patients receiving combination antiretroviral therapy are ineligible
研究组 & 干预措施
Arm I (paclitaxel, carboplatin, vorinostat)
Patients receive paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes on day 0. Patients also receive vorinostat PO once daily on days -2 to 2.
干预措施: Carboplatin (Drug)
Arm I (paclitaxel, carboplatin, vorinostat)
Patients receive paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes on day 0. Patients also receive vorinostat PO once daily on days -2 to 2.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (paclitaxel, carboplatin, vorinostat)
Patients receive paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes on day 0. Patients also receive vorinostat PO once daily on days -2 to 2.
干预措施: Paclitaxel (Drug)
Arm I (paclitaxel, carboplatin, vorinostat)
Patients receive paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes on day 0. Patients also receive vorinostat PO once daily on days -2 to 2.
干预措施: Vorinostat (Drug)
Arm II (paclitaxel, carboplatin, placebo)
Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2.
干预措施: Carboplatin (Drug)
Arm II (paclitaxel, carboplatin, placebo)
Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (paclitaxel, carboplatin, placebo)
Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2.
干预措施: Paclitaxel (Drug)
Arm II (paclitaxel, carboplatin, placebo)
Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2.
干预措施: Placebo Administration (Other)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 1 year
Estimated using the product-limit method of Kaplan and Meier. PFS defined as time from randomization to progression or death due to any cause. Progression defined as Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
次要结局
- Dose Limiting Toxicity (DLT) (Phase I)(4 weeks from start of treatment, up to 1 year)
- Maximum Tolerated Dose (MTD) (Phase I)(4 weeks from start of treatment, up to 1 year)