A Phase II Randomized Study of OSI-774 (Erlotinib) (NSC #718781) With or Without Carboplatin/Paclitaxel in Patients With Previously Untreated Adenocarcinoma of the Lung Who Never Smoked or Were Former Light Smokers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 188
- 试验地点
- 96
- 主要终点
- 18 Weeks Progression Free Survival (PFS) Rate
研究概览
简要总结
This randomized phase II trial studies how well erlotinib hydrochloride with or without carboplatin and paclitaxel works in treating patients with stage III-IV non-small cell lung cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving erlotinib hydrochloride together with carboplatin and paclitaxel may kill more tumor cells than giving either drug alone.
详细描述
PRIMARY OBJECTIVES:
I. To determine the distribution of progression-free survival (PFS) in patients with previously untreated advanced adenocarcinoma of the lung who are never or light former smokers treated with either OSI-774 (erlotinib) (erlotinib hydrochloride) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).
SECONDARY OBJECTIVES:
I. To determine the radiographic response rate in patients with previously untreated advanced adenocarcinoma of the lung who are never or light former smokers treated with either OSI-774 (erlotinib) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).
II. To determine the frequency of epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) mutations and anaplastic lymphoma kinase (ALK) translocations in patients with previously untreated advanced adenocarcinoma of the lung who are never or light former smokers.
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
- •Histologic documentation of primary lung adenocarcinoma including any variant thereof such as pure or mixed bronchioloalveolar carcinoma or adenosquamous cell carcinoma; patients with non-small cell lung cancer (NSCLC) not otherwise specified (NOS) are not eligible
- •Pathology block or unstained slides from initial or subsequent diagnosis must be available for sequencing of EGFR, K-ras, Erb-2 and B-raf; patients need to have had at least a core biopsy; patients whose diagnosis was made through a fine needle aspirate will not have sufficient material for mutational analysis and are not eligible
- •Select stage IIIB with cytologically documented malignant pleural or pericardial effusion OR stage IV disease
- •Patients must be chemotherapy naïve; they may not have received neo-adjuvant or adjuvant chemotherapy
- •No prior exposure to OSI-774 (erlotinib) or other treatments targeting the human epidermal growth factor receptor (HER) family axis (e.g., trastuzumab, gefitinib, cetuximab, lapatinib, etc.)
- •No uncontrolled central nervous system metastases (i.e., any known central nervous system [CNS] lesion which is radiographically unstable, symptomatic and/or requiring corticosteroids); patients must be >= 3 weeks beyond completing cranial irradiation and off corticosteroid therapy
- •>= 3 weeks since prior radiation therapy
- •>= 3 weeks since prior major surgery
- •No treatment with an investigational agent currently or within the last 28 days
- •Non-smoker or former light smoker; non-smoker is defined as a person who smoked =< 100 cigarettes in their lifetime while a former light smoker is a patient who smoked between > 100 cigarettes AND =< 10 pack years AND quit >= 1 year ago; this must be documented on the On-study Form (C-1405)
- •Eastern Cooperative Oncology Group (ECOG) 0 or 1
- •Non-pregnant and non-nursing
- •No dysphagia or active gastrointestinal disease or disorder that alters gastrointestinal motility or absorption; no lack of integrity of the gastrointestinal tract (e.g., a significant surgical resection of the stomach or small bowel); patients unable to swallow intact tablets must be able to swallow tablets dissolved in water
- •Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan; lesions that are considered non-measurable include the following:
- •Bone lesions
- •Leptomeningeal disease
- •Pleural/pericardial effusion
- •Lymphangitis cutis/pulmonis
- •Abdominal masses that are not confirmed and followed by imaging techniques
- •Cystic lesions
- •Granulocyte >= 1,500/mcl
- •Platelet count >= 100,000/mcl
- •Hemoglobin >= 9.0 g/dL
- •Total bilirubin =< upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x ULN
- •Creatinine =< 1.5 mg/dl
排除标准
- 未提供
研究组 & 干预措施
Arm I (erlotinib hydrochloride)
Patients receive erlotinib hydrochloride PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Erlotinib (Drug)
Arm I (erlotinib hydrochloride)
Patients receive erlotinib hydrochloride PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Erlotinib Hydrochloride (Drug)
Arm II (erlotinib hydrochloride, paclitaxel, carboplatin)
Patients receive erlotinib hydrochloride as in arm I. Patients also receive paclitaxel IV over 1-3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of 6 cycles of treatment, patients may continue to receive erlotinib hydrochloride alone as above.
干预措施: Carboplatin (Drug)
Arm II (erlotinib hydrochloride, paclitaxel, carboplatin)
Patients receive erlotinib hydrochloride as in arm I. Patients also receive paclitaxel IV over 1-3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of 6 cycles of treatment, patients may continue to receive erlotinib hydrochloride alone as above.
干预措施: Erlotinib (Drug)
Arm II (erlotinib hydrochloride, paclitaxel, carboplatin)
Patients receive erlotinib hydrochloride as in arm I. Patients also receive paclitaxel IV over 1-3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of 6 cycles of treatment, patients may continue to receive erlotinib hydrochloride alone as above.
干预措施: Erlotinib Hydrochloride (Drug)
Arm II (erlotinib hydrochloride, paclitaxel, carboplatin)
Patients receive erlotinib hydrochloride as in arm I. Patients also receive paclitaxel IV over 1-3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of 6 cycles of treatment, patients may continue to receive erlotinib hydrochloride alone as above.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
18 Weeks Progression Free Survival (PFS) Rate
时间窗: At 18 weeks
The product limit estimator developed by Kaplan Meier will be used to graphically describe progression free survival for patients randomized to each study arm. The 18 week progression-free survival rate was defined as the proportion of patients that were alive progression-free 18 weeks after registration into the study. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions. Kaplan-Meier estimate of 18-week progression-free survival was calculated.
次要结局
- Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment.(Duration of study (up to 3 years))
- Overall Response Rate(Duration of Study (up to 3 years))