A Phase II, Open-label, Multicenter Study to Evaluate the Effect of Tumor-based HER2 Activation on the Efficacy of rhuMAb 2C4 (Pertuzumab) in Subjects With Recurrent Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 7
- 主要终点
- Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)
研究概览
简要总结
The purpose of this study is to determine if the study drug pertuzumab is effective in treating patients with advanced lung cancer that has recurred following prior chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Signed informed consent
- •Tumor accessible to biopsy and willingness to undergo tumor biopsy
- •Age >= 18 years
- •Recurrent, histologically documented NSCLC, i.e., squamous cell, adeno-, or large cell anaplastic carcinoma. A cytologic diagnosis is acceptable (i.e. fine-needle aspiration or pleural fluid cytology).
- •Measurable disease with at least one lesion that can be accurately measured in at least one dimension (bilateral dimensions should be recorded). Each lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain X-ray, CT, and MRI, or >= 10 mm when measured by spiral CT.
- •Progression of disease during, or after completion of, at least one prior chemotherapy regimen, which should have contained either a platinum, a taxane or a vinca alkaloid (e.g. vinorelbine). There is no upper limit on the number of prior chemotherapy regimens each subject may have received.
- •Recovery from reversible acute effects of prior chemotherapy regimens or radiotherapy to NCI-CTC Grade <= 1 (excluding alopecia)
- •ECOG performance status of 0 or 1
- •Use of an effective means of contraception for men, or for women of childbearing potential
- •Absolute neutrophil count >= 1500/mL, platelet count of >= 75,000/mL and hemoglobin >= 9 g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbepoetin [Aranesp] is permitted)
- •Serum bilirubin <= 1.5 x the upper limit of normal (ULN) and alkaline phosphatase, AST, and ALT <= 2.5 x ULN (ALT, AST, and alkaline phosphatase <= 5 x ULN for subjects with liver metastases)
- •Serum creatinine <= 1.5 x ULN
- •Internalized normalized ratio (INR) < 1.5 and activated partial thromboplastin time (aPTT) < 1.5 ULN (except for subjects receiving warfarin)
排除标准
- •Prior treatment with any HER pathway inhibitors (e.g., Herceptin [Trastuzumab], Iressa [gefitinib], Tarceva [erlotinib hydrochloride], C225, CI1033, TAK165
- •Treatment with other experimental anti-cancer agents within 4 weeks prior to Day 1
- •Histologically documented bronchioalveolar carcinoma
- •History or clinical or radiographic evidence of central nervous system or brain metastases
- •Ejection fraction, determined by ECHO, <50%
- •Uncontrolled hypercalcemia (> 11.5 mg/dL)
- •Prior exposure of > 360 mg/m2 doxorubicin or liposomal doxorubicin, > 120 mg/m2 mitoxantrone, or > 90 mg/m2 idarubicin
- •Ongoing corticosteroid treatment, except for subjects who are on stable doses of < 20 mg of prednisone daily (or equivalent), or for subjects who are taking corticosteroids for non-malignant conditions
- •History of other malignancies within 5 years of Day 1 except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, or basal or squamous cell skin cancer
- •History of serious systemic disease, uncontrolled hypertension (diastolic blood pressure > 100 mmHg on two consecutive occasions), unstable angina, congestive heart failure, or myocardial infarction within 6 months prior to Day 1, or unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, or controlled hypertension are eligible)
- •Ongoing liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- •Active infection requiring IV antibiotics
- •Known human immunodeficiency virus infection
- •Pregnancy or lactation
- •Major surgery or significant traumatic injury within 3 weeks prior to Day 1, with the exception of tumor biopsy for the purposes of the study
- •Inability to comply with study and follow-up procedures
- •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
研究组 & 干预措施
Pertuzumab
Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Subjects received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond.
干预措施: Pertuzumab (Drug)
结局指标
主要结局
Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)
时间窗: Baseline to the end of the study (up to 1 year)
A best overall response could occur at any time during the study and was determined by Response Evaluation Criteria in Solid Tumors (RECIST). A CR was defined as the disappearance of all target lesions (TL) or the disappearance of all non-TLs and normalization of tumor marker level. A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD. SD was defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since the treatment started for TLs and the persistence of 1 or more non-TL(s) and/or the maintenance of tumor marker level above normal limits. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started or the appearance of one or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.
次要结局
- Number of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) With HER2 Phosphorylation + or - Tumors(Baseline to the end of the study (up to 1 year))
- Progression-free Survival(Baseline to the end of the study (up to 1 year))
- Number of Participants Free From Disease Progression at 3, 6, and 12 Months(Baseline to the end of the study (up to 1 year))