A PHASE 1/2, OPEN-LABEL, SINGLE ARM TRIAL TO DETERMINE THE RECOMMENDED PHASE 2 DOSE AND EVALUATE THE EFFICACY OF PF-00299804 IN PATIENTS IN KOREA WITH KRAS WILD TYPE ADVANCED NSCLC, WHICH IS REFRACTORY TO CHEMOTHERAPY AND ERLOTINIB OR GEFITINIB
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 55
- 试验地点
- 3
- 主要终点
- Recommended Phase 2 Dose (RP2D) - Phase 1
研究概览
简要总结
To assess the safety and efficacy of PF-00299804 in patients with advanced lung cancer.
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
- •Advanced NSCLC
- •Prior treatment with and failure of at least one regimen of chemotherapy and erlotinib or gefitinib
- •Prior treatment with no more than two chemotherapy regimens, including adjuvant treatment
- •Measurable disease
排除标准
- •Chemotherapy, radiotherapy, biological or investigational agents within 4 weeks of baseline disease assessment
- •Patients who lack of tolerance of erlotinib therapy
- •Patients with known brain Metastases
- •Patients with demonstrated history of or presence of interstitial lung disease.
研究组 & 干预措施
1
干预措施: PF-00299804 (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D) - Phase 1
时间窗: Baseline up to Day 21
The highest dose at which less than (\<) 33 percent (%) of participants experienced dose-limiting toxicities (DLT) was to be designated as the maximum tolerated dose (MTD) as well as the RP2D. DLT was defined as any of the following events: Grade 3/4 (severe or life-threatening/ disabling adverse event \[AE\]) nausea, vomiting, or diarrhea (despite the use of adequate/maximal medical intervention and/or prophylaxis); Grade greater than or equal to (\>=) 3 (severe or life-threatening/disabling AE or death related to AE) non-hematological toxicity; delayed (which delayed scheduled treatment for \>14 days) recovery from toxicity related to treatment with PF-00299804; Grade 4 neutropenia (absolute neutrophil count \[ANC\] \<500 cells per cubic millimeter \[cells/mm\^3\] for 5 or more consecutive days or febrile neutropenia \[fever \>=38.5 degrees Celsius with ANC \<1000 cells/mm\^3\]); and Grade 4 thrombocytopenia (\<25,000 cells/mm\^3) or bleeding which required platelet transfusion.
Progression-Free Survival (PFS) at Month 4 (PFS4m) - Phase 2
时间窗: Month 4
PFS4m was defined as percent chance of being event free (event defined as progressive disease \[PD\] or death due to any cause, whichever occurred first) at 4 months. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST), as at least 20 percent (%) increase in the sum of longest dimensions (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
次要结局
- Progression-Free Survival (PFS) at Month 6 (PFS6m) - Phase 2(Month 6)
- Overall Survival (OS) at Month 6 (OS6m) - Phase 2(Month 6)
- Percentage of Participants With Objective Response - Phase 1(Baseline until disease progression or initiation of new anti-cancer therapy or death, assessed every 2 (odd-numbered) cycles up to 12 months after end of treatment (EOT) (EOT: up to Day 506))
- Soluble Protein Biomarkers Level(Cycle 1 Day 1 (C1D1, Baseline), Day 1 of each odd-numbered cycle up to Cycle 17 for both Phase 1 and Phase 2)
- Number of Participants With Epidermal Growth Factor Receptor (EGFR), Kirsten Rat Sarcoma (KRAS), and Human Epidermal Growth Factor Receptor-2 (HER2) Mutation Status(Screening)
- Maximum Observed Plasma Concentration (Cmax) of PF-00299804 30 mg and PF-00299804 45 mg(0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9 for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-00299804 30 mg and PF-00299804 45 mg(0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on Cycle 0 Day -9 (C0D-9) for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2)
- Plasma Decay Half-Life (t1/2) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1(0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on Cycle 0 Day -9 (C0D-9))
- Area Under the Curve From Time Zero to 24 Hour Post-Dose (AUC0-24) of PF-00299804 30 mg and PF-00299804 45 mg(0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on Cycle 0 Day -9 (C0D-9) for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-00299804 30 mg and PF-00299804 45 mg- Phase 1(0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9)
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1(0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9)
- Accumulation Ratio (Rac) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1(0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C0D-9, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14)
- Average Plasma Concentration (Cavg) of PF-00299804 30 mg and PF-00299804 45 mg(0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2)
- Linearity Ratio (Rss) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1(0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14)
- Minimum Observed Plasma Trough Concentration (Ctrough) of PF-00299804 30 mg and PF-00299804 45 mg(0 hours (pre-dose) on C2D1, C3D1, C4D1)
- Number of Participants With Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Phase 2(Baseline up to end of treatment (up to Day 889))
- Number of Participants With Change in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Phase 2(Baseline up to end of treatment (up to Day 889))
- Dermatology Life Quality Index (DLQI) Total Score - Phase 2(C1D1 (baseline), D1 of each subsequent cycle up to C44)
- Best Overall Response (BOR) - Phase 2(Baseline until disease progression or initiation of new anti-cancer therapy or death, assessed every 2 (odd-numbered) cycles up to 12 months after EOT (EOT: up to Day 1723))
- Duration of Response (DR)(Baseline until disease progression or initiation of new anti-cancer therapy or death, assessed every 2 (odd-numbered) cycles up to 12 months after EOT (EOT: up to Day 506 for Phase 1 and up to Day 1723 for Phase 2))