Phase Ib, Open-label, Multi-center Study of the Combination of Pertuzumab and Erlotinib in Patients With Locally Advanced or Metastatic (Stage IIIb/IV) NSCLC After Failure of at Least One Prior Chemotherapy Regimen.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 主要终点
- Percentage of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This study will assess the safety and tolerability, and make a preliminary assessment of activity, of a combination of pertuzumab and erlotinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have failed on at least one prior chemotherapy regimen. The anticipated time on study treatment is until disease progression or unacceptable toxicity, and the target sample size is less than 100 individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Adult patients greater than or equal to 18 years of age
- •Histological confirmation of non-small cell lung cancer (NSCLC)
- •Locally advanced or metastatic disease
- •Failure of at least one prior regimen of standard chemotherapy for locally advanced or metastatic disease
- •Life expectancy of more than or equal to 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Baseline Left Ventricular Ejection Fraction (LVEF) of greater than or equal to 50%
- •A negative pregnancy test one week prior to treatment and willingness to use contraception among women of childbearing potential
- •Availability of histological Formalin-Fixed, Paraffin-Embedded (FFPE) tumor tissue
排除标准
- •Prior chemotherapy, radiotherapy or immunotherapy within 4 weeks of study Day -8
- •Prior treatment with any agent which targets growth factors or their receptors
- •Patients who have not recovered from the acute reversible effects of chemotherapy and radiotherapy
- •History of clinically significant cardiovascular disease
- •History or evidence of central nervous system metastases
- •Treatment with any investigational drug within 28 days of the start of the study (day -8)
- •Prior cumulative doxorubicin dose of more than 360 mg/m2 or the equivalent
研究组 & 干预措施
Cohort 1
Participants will receive IV infusion of pertuzumab at a loading dose of 840 mg on Day 1, followed by a dose of 420 mg every 3 weeks. Erlotinib will be administered daily, at a dose level of 100 mg orally (PO).
干预措施: Erlotinib (Drug)
Cohort 1
Participants will receive IV infusion of pertuzumab at a loading dose of 840 mg on Day 1, followed by a dose of 420 mg every 3 weeks. Erlotinib will be administered daily, at a dose level of 100 mg orally (PO).
干预措施: Pertuzumab (Drug)
Cohort 2
Participants will receive IV infusion of pertuzumab at a loading dose of 840 mg on Day 1, followed by a dose of 420 mg every 3 weeks. Erlotinib will be administered daily, at a dose level of 150 mg orally (PO).
干预措施: Erlotinib (Drug)
Cohort 2
Participants will receive IV infusion of pertuzumab at a loading dose of 840 mg on Day 1, followed by a dose of 420 mg every 3 weeks. Erlotinib will be administered daily, at a dose level of 150 mg orally (PO).
干预措施: Pertuzumab (Drug)
结局指标
主要结局
Percentage of Participants With Dose Limiting Toxicities (DLTs)
时间窗: From baseline to end of the study (up to 42 weeks)
A DLT was defined as: Any non-hematological toxicity ≥ Grade 3 according to the Common Terminology Criteria for Adverse Events, version 3.0, except for fever, chills, and flu-like symptoms, which occurred despite adequate participant management. The following Grade 1-3 toxicities were exempt: Grade 1-3 skin and/or epithelial toxicities consistent with erlotinib single agent therapy, unless they did not respond to treatment or dose reduction or interruption (Grade 4 skin and/or epithelial toxicities were considered to be a DLT); Grade 4 neutropenia occurring for \> 7 days; febrile neutropenia which occurred despite adequate participant management; Grade 4 thrombocytopenia or any thrombocytopenia requiring platelet transfusion; and any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.
次要结局
- Percentage of Participants Classified as Responders(within 18 weeks)
- Percentage of Participants With a Complete Response or Partial Response at the End of Cycles 1, 2, 3, 4, and 6(From baseline to the end of the study (up to 42 weeks))
- Peak Plasma Concentration (Cmax) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)
- Time of Cmax (Tmax) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)
- Area Under the Plasma Concentration Versus Time Curve (AUC) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With Non-small Cell Lung Cancer (NSCLC)(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)
- Volume of Distribution at Steady-state (Vss) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)
- Clearance (CL) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)
- Terminal Phase Plasma Half-life (t ½) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)