A Randomized, Double-Blind Phase 2 Study of Ruxolitinib or Placebo in Combination With Pemetrexed/Cisplatin and Pemetrexed Maintenance for Initial Treatment of Subjects With Nonsquamous Non-Small Cell Lung Cancer That Is Stage IIIB, Stage IV, or Recurrent
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 76
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The purpose of this study was to determine if ruxolitinib, in combination with Pemetrexed/Cisplatin and Pemetrexed Maintenance, is safe and effective in the treatment of nonsquamous non-small cell lung cancer (NSCLC) that is Stage IIIB, Stage IV, or recurrent.
详细描述
The study consisted of an open-label, safety run-in (consisting of 1 to 4 cohorts of 9 participants each), to confirm the safety of ruxolitinib in combination with pemetrexed/cisplatin in participants with nonsquamous non-small cell lung cancer (NSCLC) that is Stage IIIB, Stage IV, or recurrent. Participants in the safety run-in received open-label ruxolitinib and pemetrexed and cisplatin.
In the second part of the study, participants enrolled and randomized and received pemetrexed and cisplatin (open-label) and either ruxolitinib or placebo in a blinded manner. The dose of ruxolitinib administered was determined from the data produced in the safety run-in phase.
Treatment consisted of repeating 21-day cycles. Participants received infusions of pemetrexed and cisplatin on Day 1 of each cycle and ruxolitinib/placebo was self-administered during the entire cycle. Maintenance therapy with ruxolitinib or placebo in combination with pemetrexed, based on the original treatment assignment, was allowed for participants eligible for maintenance therapy.
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
- Double (Participant, Investigator)
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
- •Histologically or cytologically confirmed diagnosis of nonsquamous NSCLC that is Stage IIIB Stage IV, or recurrent after prior definitive intervention (radiation, surgery, or chemoradiation therapy, with or without adjuvant or neoadjuvant chemotherapy).
- •Radiographically measurable or evaluable disease.
- •Life expectancy of at least 12 weeks.
- •Tumor without activating driver mutations for which there is available therapy (eg, tumor without mutations in epidermal growth factor receptor or anaplastic lymphoma).
- •An modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:
- •Criteria:
- •C-reactive protein >10 mg/L AND albumin ≥35 g/L; Score = 1
- •C-reactive protein >10 mg L AND albumin <35 g/L; Score = 2
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Adequate renal, hepatic, and bone marrow function demonstrated by protocol-specified laboratory parameters at the screening visit.
排除标准
- •Squamous or mixed histology (eg, adenosquamous) NSCLC
- •Previous systemic therapy for advanced or metastatic disease.
- •Known active central nervous system (CNS) metastases.
- •Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval.
- •Current uncontrolled cardiac disease such as angina or myocardial infarction, congestive heart failure including New York Heart Association functional classification of 3, or arrhythmia requiring treatment.
- •Uncontrolled concomitant medical conditions, including, but not limited to, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric diseases.
研究组 & 干预措施
Ruxolitinib plus Pemetrexed/Cisplatin
干预措施: Ruxolitinib (Drug)
Ruxolitinib plus Pemetrexed/Cisplatin
干预措施: Pemetrexed (Drug)
Ruxolitinib plus Pemetrexed/Cisplatin
干预措施: Cisplatin (Drug)
Placebo plus Pemetrexed/Cisplatin
干预措施: Placebo (Drug)
Placebo plus Pemetrexed/Cisplatin
干预措施: Pemetrexed (Drug)
Placebo plus Pemetrexed/Cisplatin
干预措施: Cisplatin (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Randomization until death due to any cause; up to 16 months or data cutoff 11FEB2016.
Overall survival is defined as the time from randomization to death due to any cause. Participants without death observed at the time of the analysis were censored at last date known to be alive. The median overall survival time was estimated using the Kaplan-Meier method. Overall survival was compared between treatment groups using log-rank test.
次要结局
- Progression-free Survival (PFS)(Randomization to disease progression, or death due to any cause if sooner; up to 16 months or to the data cutoff 11FEB2016.)
- Objective Response Rate (ORR)(Baseline through end of study; up to 16 months or to the data cutoff 11FEB2016.)
- Duration of Response(From the start of response to the end of response; up to 16 months or to the data cutoff 11FEB2016.)
- Participants With Treatment-emergent Adverse Events (TEAEs)(Baseline through approximately 30 days post treatment discontinuation; up to 16 months or to the data cutoff 11FEB2016.)