Phase II Randomized Open-Label Trial of the EGFR Tyrosine Kinase Inhibitor OSI-774 (Tarceva™) in Combination With Paclitaxel and Carboplatin Prior to Surgery in Resectable Stage IIIA (N2) and IIIB (T4 N2) NSCLC: A Clinical Outcome and Biological Endpoint Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Number of Patients With Response
研究概览
简要总结
The goal of this clinical research study is to learn about the safety and effectiveness of OSI-774 when combined with standard chemotherapy (carboplatin and paclitaxel) before surgery in the treatment of non-small cell lung cancer.
详细描述
This is a phase II, single institution open label randomized trial of induction carboplatin and paclitaxel plus/minus daily oral OSI-774 in patients with potentially resectable NSCLC that is stage IIIA and IIIB (T4 satellite nodules or invasion into T4 structures but no malignant effusion.) N3 disease is excluded. Patients will be required to have pathologically demonstrated N2 disease via mediastinoscopy. Forty patients will be treated with 3 courses of chemotherapy followed by surgery. Ten of these patients will be randomized to chemotherapy alone and 30 patients to chemotherapy plus OSI-774. The 10 patients will serve as a chemotherapy alone control for molecular endpoint analysis. OSI-774 will be stopped the night before surgery. At the time of surgery, pathologic response will be determined. Following surgery, patients will be treated with consolidation radiation therapy if there are positive margins or N2 lymph nodes at the time of resection. Patients who have no N2 disease at surgery will have the option of consolidation radiation therapy but will not be required to have it done. Patients not able to tolerate radiation even if they have N2 disease or positive margins at surgery may continue on this study. This will be followed by maintenance OSI-774 for patients from both arms of the study. OSI-774 will be continued as maintenance to a maximum of 2 years following surgery. Tissue for molecular studies will be obtained pretreatment either at the time of diagnostic biopsy or mediastinoscopy. Post-treatment tissue will be obtained at the time of surgery. This tissue will be assayed for defined molecular endpoints using immunohistochemistry, immunoprecipitation and mRNA expression analysis. Blood, urine, hair follicles, and skin samples will also be collected from patients who consent to provide these.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have signed consent for LAB03-0383
- •Pathologic documentation of NSCLC
- •Stage IIIA and IIIB (T4 satellite nodules or invasion into T4 structures but no malignant effusion) with all patients requiring mediastinoscopy positive N2, potentially resectable disease. N3 disease is excluded.
- •Measurable disease
- •Zubrod performance status of 0 or 1
- •Calculated post-resectional FEV1 of > 40%
- •WBC>4000/l, ANC>1500/l, platelets > 100,000/l
- •Serum creatinine < 1.5 ULN or calculated creatinine > 50 cc/min
- •Total serum bilirubin <1.5 x ULN or SGPT or SGOT < 2 X ULN
- •The following must be completed within 28 days of registration: CT scan of the chest and upper abdomen to include the adrenals. Mediastinoscopy to document ipsilateral nodal involvement and exclude N3 disease Blood tests, and pulmonary function tests The following must be completed within 2 months of registration: Pet scan If a CT PET is done more than 28 days, only the CT needs to be repeated and a bone scan to rule out bone metastases
排除标准
- •No prior chemotherapy or radiation for NSCLC
- •No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient has been disease-free for at least five years. If patient is suspected or known to have basal or squamous skin cancer, this maybe treated after induction chemotherapy is completed at the time of thoracotomy.
- •No post-obstructive pneumonia or other serious infection or other serious underlying medical condition that would impair ability of patient to receive protocol treatment, including prior allergic reactions to drugs containing cremophor.
- •Pregnant or nursing women may not participate
研究组 & 干预措施
Chemotherapy + Tarceva
干预措施: Tarceva (OSI-774) (Drug)
Chemotherapy + Tarceva
干预措施: Paclitaxel (Drug)
Chemotherapy + Tarceva
干预措施: Carboplatin (Drug)
Chemotherapy Alone
干预措施: Paclitaxel (Drug)
Chemotherapy Alone
干预措施: Carboplatin (Drug)
结局指标
主要结局
Number of Patients With Response
时间窗: 5 Years to collect outcome information
Response defined by tumor assessment using Response Evaluation Criteria In Solid Tumors (RECIST) to learn effectiveness of Tarceva (OSI-774) when combined with standard chemotherapy before surgery.
次要结局
未报告次要终点