Randomized, Phase II, Open-Label Controlled Study of Two Different Doses and Schedules of EMD 72000 (Matuzumab) in Combination With Pemetrexed, or Pemetrexed Alone, as Second-Line Treatment for Stage IIIB/IV Non-Small Cell Lung Cancer and Progressive Disease on or After First-Line Treatment With a Platinum in Combination With Taxanes, Gemcitabine and Vinorelbine
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- EMD Serono
- 入组人数
- 150
- 试验地点
- 43
- 主要终点
- Number of Participants With Objective Response Assessed by Independent Review Committee
研究概览
简要总结
This open-label, multicenter, randomized, controlled, Phase II study is planned to answer questions about how the drug, matuzumab (EMD 72000), works and is part of an effort aimed to develop better treatment for advanced lung cancer by combining matuzumab, a monoclonal antibody, with a chemotherapy treatment, called pemetrexed.
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
- 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
- •Written informed consent provided prior to any screening procedure
- •Male or female, greater than (>) 18 years of age
- •Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
- •Demonstrated PD on or after first-line chemotherapy for Stage IIIB/IV disease. The first-line therapy must consist of platinum-based regimens in combination with taxanes, gemcitabine or vinorelbine. Stage IIIB/IV participants must have measurable disease (tumor) without clinically significant pleural effusion unless the pleural effusion can be effectively drained prior to admission into the study
- •A chemotherapy-free interval of at least 3 weeks between the end of first-line chemotherapy and start of study treatment
- •At least 1 measurable lesion according to the modified World Health Organization (WHO) criteria
- •Archived tissue or cytologic sample available for the determination of epidermal growth factor receptor (EGFR) expression
- •Eastern cooperative oncology group (ECOG) performance status 0-1
- •Life expectancy >12 weeks
- •Adequate baseline organ functions, defined as: Serum creatinine less than or equal to (≤)1.5*upper limit of normal (ULN). In case of borderline values for serum creatinine, creatinine clearance must be greater than or equal to (≥) 45 millimeters per minute (mL/min); Total bilirubin <1.5*ULN; Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5*ULN (participants with liver metastases should have ALT/AST <5*ULN.); Absolute neutrophil count ≥1500per cubic millimeter(mm^3); Platelet count ≥100000/mm^3; Hemoglobin level ≥10 grams per deciliter
- •If procreative potential (male or female), willingness to use effective contraceptive methods for the duration of treatment and continuing for 2 months after the last dose. Participants of procreative potential are defined as any fertile male, or any female who has experienced menarche and who is not postmenopausal (defined as age-related amenorrhea ≥12 months) or who has not undergone successful surgical sterilization (hysterectomy or bilateral oophorectomy)
排除标准
- •Radiotherapy or major surgery within 30 days prior to the start of study treatment
- •Prior treatment with an EGFR-directed therapy or with EGFR signal transduction inhibitors
- •Prior treatment with pemetrexed
- •Pregnant (confirmed by beta-human chorionic gonadotropin [β-HCG]) or lactating female
- •Weight loss >10% within 12 weeks prior to the start of study treatment
- •Documented or symptomatic brain metastases or leptomeningeal disease
- •Myocardial infarction within 6 months prior to the start of study treatment, uncontrolled congestive heart failure, or any current New York Heart Association Grade III or IV cardiovascular disorder despite treatment
- •Presence of a Grade ≥2 preexisting skin disorder (except for alopecia)
- •Previous diagnosis of autoimmune disease with significant organ involvement
- •Concurrent malignancies or invasive carcinomas diagnosed within the past 5 years, except for adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix
- •Any significant disease that, in the Investigator's opinion, should exclude the participant from the study
- •History of significant neurologic or psychiatric disorder (for example, dementia, seizures, or bipolar disorder)
- •History of drug abuse within 6 months prior to the start of study treatment
- •Known conditions that require concurrent treatment with a nonpermitted drug
- •Presence of a contraindication to the study treatment(s) according to the current Investigator's Brochure (IB) for matuzumab and the labeling for pemetrexed
- •Known hypersensitivity to the study treatment or any of its components
- •Participation in another clinical study within 30 days prior to the start of study treatment
研究组 & 干预措施
Pemetrexed Alone
Participants will receive pemetrexed 50 milligrams per square meter (mg/m^2) intravenous (IV) infusion every 3 weeks until disease progression (PD) or the occurrence of unacceptable toxicity.
干预措施: Pemetrexed (Drug)
Pemetrexed Plus Matuzumab 800 mg per Week
Participants will receive pemetrexed 50 mg/m^2 IV infusion every 3 weeks in combination with matuzumab 800 milligrams (mg) IV infusion once every week. Treatment will continue until PD or the occurrence of unacceptable toxicity.
干预措施: Pemetrexed (Drug)
Pemetrexed Plus Matuzumab 800 mg per Week
Participants will receive pemetrexed 50 mg/m^2 IV infusion every 3 weeks in combination with matuzumab 800 milligrams (mg) IV infusion once every week. Treatment will continue until PD or the occurrence of unacceptable toxicity.
干预措施: Matuzumab (Drug)
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Participants will receive pemetrexed 50 mg/m^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. Treatment will continue until PD or the occurrence of unacceptable toxicity.
干预措施: Pemetrexed (Drug)
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Participants will receive pemetrexed 50 mg/m^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. Treatment will continue until PD or the occurrence of unacceptable toxicity.
干预措施: Matuzumab (Drug)
结局指标
主要结局
Number of Participants With Objective Response Assessed by Independent Review Committee
时间窗: Baseline up to PD or death due to any cause (up to approximately 2 years)
Objective response was defined as having a complete response (CR) or a partial response (PR). Response assessment was performed using modified World Health Organization (WHO) criteria. Complete response: disappearance of all index and non-index lesions, without appearance of any new lesion. PR: greater than (\>) 50 percent (%) decrease from baseline in sum of product of diameters of index lesions, without appearance of any new lesion.
次要结局
- Duration of Objective Response Assessed by Independent Review Committee(From first documented objective response to PD or death due to any cause (up to approximately 3.5 years))
- Progression-Free Survival (PFS)(Baseline up to PD or death due to any cause (up to approximately 3.5 years))
- Overall Survival (OS)(Baseline up to PD or death due to any cause (up to approximately 3.5 years))
- Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS)(Baseline, Cycle 2 (Cycle length = 3 weeks))