A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Oral Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) in Patients With Advanced Malignant Pleural Mesothelioma Previously Treated With Systemic Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 661
- 主要终点
- Number of Participants Who Discontinued Study Treatment Due to an AE
研究概览
简要总结
The goal of this study is to assess the efficacy and safety of an oral investigational drug suberoylanilide hydroxamic acid (vorinostat, MK-0683) compared to placebo, in the treatment of participants with advanced malignant pleural mesothelioma who have failed at least one prior chemotherapy regimen. The primary hypotheses are the following: (1) vorinostat improves overall survival (OS) compared to placebo (2) vorinostat is generally safe and well tolerated.
详细描述
Treatment Extension Phase: Participants in this study will be eligible to enroll in an open-label treatment extension phase if they: a) were originally randomized to the vorinostat arm and have not experienced disease progression; b) were randomized to the placebo arm and meet the "Extension Phase Inclusion Criteria for Participants in the Placebo Arm" below; or c) were originally randomized to the vorinostat arm and discontinued study therapy for reasons other than progression and the investigator believes that it is in the participant's best interest to resume vorinostat treatment.
As specified by the protocol, based on planned extension phase inclusion criteria and pre-specified primary outcome analyses requirements, the extension phase of this study was not conducted.
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
- Triple (Participant, 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
- •Participants who are receiving treatment with vorinostat and have not experienced progression of mesothelioma
- •Randomized to the placebo arm and: 1) have a Karnofsky performance scale status of ≥70; and 2) have adequate bone marrow, liver, and kidney function and adequate coagulation (per prespecified laboratory values)
- •Randomized to vorinostat and have discontinued study therapy for reasons other than progression of mesothelioma, if the investigator is of the opinion that the potential benefit outweighs potential risks associated with using vorinostat
排除标准
- •Has an active infection for which they received treatment with intravenous antibiotic, antiviral, or antifungal medications within 2 weeks of the start of study drug.
- •Has a "currently active" second malignancy; a malignancy is not considered "currently active" if participants have completed therapy for the second malignancy and are disease free from prior malignancies for >5 years
- •Has uncontrolled brain metastases
- •Has a known human immunodeficiency virus (HIV) infection or HIV-related malignancy
- •Is pregnant or breast feeding
- •Has a history of gastrointestinal surgery or other procedures that might interfere with the absorption or swallowing of the study drug
研究组 & 干预措施
Vorinostat
Vorinostat three 100 mg capsules twice daily for 3 consecutive days of treatment followed by 4 days of rest repeated weekly, in 21-day cycles. Treatment will continue until disease progression or unacceptable toxicity.
干预措施: Vorinostat (Drug)
Placebo
Placebo capsules twice daily for 3 consecutive days of treatment followed by 4 days of rest repeated weekly, in 21-day cycles. Treatment will continue until disease progression or unacceptable toxicity.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)
An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. The final analysis for participants who discontinued study treatment due to an AE was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. Per protocol number of participants who discontinued study treatment due to an AE is reported here for all randomized participants who received ≥1 dose of study treatment. As specified by the protocol, participants who discontinued study treatment due to an AE remained on study until investigator notification to discontinue.
Overall Survival (OS)
时间窗: Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of final analysis were censored at the date of the last follow up. The final analysis for OS was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. OS analysis is reported here for all randomized participants.
Number of Participants Who Experienced Adverse Events (AEs) Characterized as Grade 3 or Grade 4 According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
时间窗: Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)
An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. Reporting of AEs per NCI CTCAE is based on 5 grades of severity; Grade 1 (mild; no treatment needed), Grade 2 (moderate; minimal treatment needed), Grade 3 (severe, not life threatening; hospitalization needed), Grade 4 (life threatening; urgent treatment needed) and Grade 5 (death).The final analysis for Grade 3 or 4 AEs was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. Per protocol number of participants who experienced Grade 3/4 AEs per NCI CTCAE is reported here for all randomized participants who received ≥1 dose of study treatment.
Number of Participants Who Experienced an AE
时间窗: Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)
An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. The final analysis for participants who experienced an AE was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. Per protocol number of participants who experienced an AE is reported here for all randomized participants who received ≥1 dose of study treatment.
次要结局
- Objective Response Rate (ORR)(Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011))
- Percentage of Participants With ≥10% Change From Baseline in FVC at Week 12(Baseline, Week 12)
- Progression Free Survival (PFS)(Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011))
- Percent Change From Baseline in Lung Cancer Symptom Scale, Modified for Mesothelioma (LCSS-Meso) Dyspnea Score at Week 12(Baseline, Week 12)
- Percentage of Participants With ≥50% Change Together With a >10 mm Change From Baseline in the LCSS-Meso Dyspnea Score at Week 12(Baseline, Week 12)
- Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 12(Baseline, Week 12)