An Open-label Phase II Multicenter Study of the Safety and Activity (as Measured by FDG-PET Imaging Changes) of the Combination of Erlotinib and Pertuzumab in Patients With Relapsed Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 主要终点
- Percentage of Patients With a 2-deoxy-2-[18F]Fluoro-D-glucose-positron Emission Tomography (FDG-PET) Response at Day 56 in All Patients and in Epidermal Growth Factor Receptor (EGFR) Mutant and Wild-type Subgroups
研究概览
简要总结
This was a Phase II, open-label, single-arm, single-stage, multicenter trial in patients with relapsed non-small cell lung cancer (NSCLC), with the objective of assessing the activity of the combination of erlotinib and pertuzumab on the basis of the endpoint of FDG-PET response rate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Histologically confirmed non-small cell lung cancer (NSCLC).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or
- •Recurrent or progressive disease after receiving at least 1, but no more than two, chemotherapy regimens for advanced or metastatic NSCLC.
- •Recovery from reversible acute effects of prior anti-cancer therapy (chemotherapy, radiotherapy, or investigational treatment) to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade ≤ 1 (excluding alopecia).
- •Ability to comply with the study and follow-up procedures, including all specified imaging studies.
- •Ability to take oral medication.
- •Life expectancy ≥ 3 months.
- •Measurable disease on computed tomography (CT).
- •At least 1 extracerebral lesion on 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) scan that is suitable for response assessment, that is measurable, and ≥ 15 mm on CT.
- •Left ventricular ejection fraction (LVEF) ≥ 50%, as determined by echocardiogram or MUltiple Gated Acquisition (MUGA) scan.
- •For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner.
- •Availability and willingness to provide sufficient tumor tissue for testing for epidermal growth factor receptor (EGFR) mutations, and other human epidermal growth factor receptor (HER) pathway and NSCLC-related biomarkers.
排除标准
- •Prior treatment with an investigational or marketed agent for the purpose of inhibiting HER family members (including HER1, HER2, HER3, and HER4). This includes, but is not limited to erlotinib, gefitinib, pertuzumab, cetuximab, and panitumumab.
- •Chemotherapy, radiotherapy, or investigational treatment within 28 days of start of study (ie, prior to Day 0) or from which patients have not yet recovered.
- •Inability to take oral medications, disease affecting gastrointestinal absorption, or prior surgical procedure affecting gastrointestinal absorption.
- •Uncontrolled diabetes.
- •Clinical or radiographic evidence of new or progression of pre-existing central nervous system (CNS) metastases.
- •Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders; ulcers; or bone fractures).
- •Current uncontrolled hypertension or unstable angina.
- •History of congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia).
- •History of myocardial infarction within 6 months of enrollment or history of unstable angina.
- •Any evidence of an unstable infection as suggested by an infectious process, coupled with hypotension and/or tachycardia and/or fever and/or positive blood culture.
- •Known human immunodeficiency virus (HIV) infection.
- •Uncontrolled hypercalcemia.
- •Pregnancy or lactation.
- •History of another malignancy in the past 2 years, unless the malignancy has been adequately treated, is currently not detectable, and is associated with a 5-year survival > 90%.
- •Claustrophobia.
- •Any other disease, condition, physical examination finding, or clinical laboratory finding that, in the opinion of the investigator, makes the patient inappropriate for the study.
研究组 & 干预措施
Pertuzumab + erlotinib
Patients received pertuzumab 840 mg intravenously (IV) 1 time (loading dose) followed by 420 mg IV (maintenance dose) every 3 weeks (q3w) plus erlotinib 150 mg orally once a day which was reduced to 100 mg orally once a day in a protocol amendment dated 19 May 2010.
干预措施: Pertuzumab (Drug)
Pertuzumab + erlotinib
Patients received pertuzumab 840 mg intravenously (IV) 1 time (loading dose) followed by 420 mg IV (maintenance dose) every 3 weeks (q3w) plus erlotinib 150 mg orally once a day which was reduced to 100 mg orally once a day in a protocol amendment dated 19 May 2010.
干预措施: Erlotinib (Drug)
结局指标
主要结局
Percentage of Patients With a 2-deoxy-2-[18F]Fluoro-D-glucose-positron Emission Tomography (FDG-PET) Response at Day 56 in All Patients and in Epidermal Growth Factor Receptor (EGFR) Mutant and Wild-type Subgroups
时间窗: Baseline to Day 56
The assessment of FDG-PET response was performed by a central reading site. PET response was based on the maximum standard uptake value (SUVmax) of up to 5 regions of interest (ROI). The tumor ROIs were identified for each patient on pretreatment FDG-PET scans and corresponded to a subset of the target lesions identified for Response Evaluation Criteria for Solid Tumors (RECIST) analysis. Specifically, the SUVmax of each ROI on the on-treatment scans was compared with the SUVmax on the corresponding pretreatment scan and the percent change was calculated. When there was more than 1 ROI, the overall percent change in SUVmax was the arithmetic mean of the percent changes in SUVmax for each of the ROIs (mSUVmax). An PET response is defined as a decrease of ≥ 20% in mSUVmax. EGFR mutation status was assessed in tumor tissue samples taken from each patient.
次要结局
- Progression-free Survival (PFS)(Baseline to the end of the study (up to 3 years))
- Overall Survival (OS)(Baseline to the end of the study (up to 3 years))
- Percentage of Patients With an Objective Response (OR)(Baseline to the end of the study (up to 3 years))
- Percentage of Patients With Disease Control (DC) at Day 56(Baseline to Day 56)