Phase 2 Open Label Trial Of Oral Intermittent Dacomitinib In Patients With Advanced Nsclc
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 41
- 试验地点
- 14
- 主要终点
- Best Overall Response (BOR) in Participants With T790M Mutation
研究概览
简要总结
This is a Phase 2 study of oral dacomitinib given every 12 hours over days 1-4 of each two-week cycle to patients with Non-small cell lung cancer. The study includes two groups of patients, those whose tumor has a documented T790M mutation, and those without this mutation. All patients will receive repeated cycles of dacomitinib until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Evidence of histologically confirmed, advanced NSCLC (stage IIIB/IV).
- •Evidence of T790M mutation to enroll in Cohort A.
- •Evidence of measurable disease by radiographic technique.
- •Adequate organ function.
排除标准
- •Patients with T790M mutation who stopped any prior EGFR-directed therapy without evidence of disease progression.
- •Symptomatic brain metastases.
- •Uncontrolled or significant cardiovascular disease.
- •Pregnant or breastfeeding.
研究组 & 干预措施
Cohort B
Patients with NSCLC. No requirement of a specific molecular signature, but excluding known T790M mutations.
干预措施: Dacomitinib (Drug)
Cohort A
Patients with NSCLC whose tumor has a documented T790M mutation in exon 20 of the Epidermal Growth Factor Receptor.
干预措施: Dacomitinib (Drug)
结局指标
主要结局
Best Overall Response (BOR) in Participants With T790M Mutation
时间窗: From baseline until disease progression, up to 61 weeks.
BOR was best response from start of treatment until disease progression, according to the RECIST,v1.1. CR=disappearance of all preexisting lesions except nodal disease, with all nodal lesions decreased to normal size (short axis \<10 mm) and no appearance of new unequivocal malignant lesions. PR= ≥30% decrease from baseline of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. CR and PR were confirmed on a follow-up imaging assessment ≥4 weeks after the initial response documentation. Progression= ≥20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions. Stable disease=not qualify for CR, PR or progression. BOR was analyzed only for participants with T790M mutation according to the primary study objective.
Objective Response Rate (ORR) in Participants With T790M Mutation
时间窗: From baseline to disease progression, up to 61 weeks.
ORR was calculated as the percentage of participants with a confirmed CR or PR relative to the total number of participants enrolled. Response Evaluation Criteria in Solid Tumors (RECIST), version (v) 1.1 were used to define CR and PR. CR=disappearance of all preexisting lesions except nodal disease, with all nodal lesions decreased to normal size (short axis \<10 mm) and no appearance of new unequivocal malignant lesions. PR= ≥30% decrease from baseline of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. CR and PR were confirmed on a follow-up imaging assessment ≥4 weeks after the initial response documentation. ORR was analyzed only for participants with T790M mutation according to the primary study objective.
次要结局
- Disease Control Rate (DCR) for Participants With T790M Mutation(From baseline to baseline to disease progression, up to 61 weeks.)
- Maximum Plasma Concentration (Cmax) for Dacomitinib and PF-05199265(Pre-dose (hour 0), 2, 4, 6, 8, and 10 hours post-dose on Day 4, Cycle 0.)
- Time to Maximum Plasma Concentration (Tmax) for Dacomitinib and PF-05199265(Pre-dose (hour 0), 2, 4, 6, 8, and 10 hours post-dose on Day 4, Cycle 0.)
- Duration of Response in Participants With T790M Mutation(From baseline to date of disease progression or death, up to 61 weeks.)
- Progression-free Survival(From baseline to disease progression or death, up to 61 weeks.)
- Progression-free Survival at 4 Months(Month 4)
- Changes From Time-matched Baseline in Adjusted Fridericia Corrected QT Interval (QTcF) on Echocardiogram (ECG)(From Baseline to Cycle 0, Day 4)