A Phase I Study Of OSI-774 (NSC #718781)-Based Multimodality Therapy For Inoperable Stage III Non Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- MTD defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity assessed using NCI CTCAE version 3.0
研究概览
简要总结
Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib and radiation therapy with combination chemotherapy may kill more tumor cells. Phase I trial to study the effectiveness of combining erlotinib and radiation therapy with combination chemotherapy in treating patients who have inoperable stage III non-small cell lung cancer
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of erlotinib that can be administered with chest radiotherapy in combination with cisplatin and etoposide or carboplatin and paclitaxel in patients with inoperable stage III non-small cell lung cancer.
II. Determine the dose-limiting toxicity of these regimens in these patients. III. Assess the clinical response (complete response, partial response, progressive disease, or stable disease) in patients treated with these regimens.
IV. Determine levels of tumor epidermal growth factor expression in patients treated with these regimens.
OUTLINE: This is a multicenter, dose-escalation study of erlotinib. Patients are assigned to 1 of 2 treatment groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
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
- •Squamous cell carcinoma
- •Adenocarcinoma (including bronchoalveolar)
- •Large cell carcinoma (including giant and clear cell carcinomas)
- •Stage IIIA (T1 or T2, N2) or IIIB disease not amenable to resection or surgery
- •T3, N2 or T4, N0-N2 disease also allowed if based on the closeness to the carina, invasion of the mediastinum, or invasion of the chest wall
- •T3, N0-N1 disease allowed provided the disease is not amenable for surgical resection
- •No M1 disease
- •No disease invasion of a vertebral body
- •Tumors adjacent to a vertebral body allowed provided all gross disease can be encompassed in the radiotherapy boost field and there is no bone invasion
- •Contralateral mediastinal disease (N3) allowed if all gross disease can be encompassed in the radiotherapy boost field
- •Pleural effusion that is transudative, cytologically negative, and non-bloody allowed if the tumor can be encompassed in a reasonable field of radiotherapy
- •No exudative, bloody, or cytologically malignant effusions
- •Effusions present on CT scans but not on chest x-ray (CXR) and too small for thoracentesis are allowed
- •Measurable or evaluable disease
- •Pleural effusions are not considered measurable or evaluable
- •Measurable disease is defined as any mass in 2 perpendicular diameters by CXR, CT scan, or MRI
- •Evaluable disease includes lesions apparent on CXR or CT scan that are:
- •Ill-defined masses associated with post-obstructive changes
- •Mediastinal or hilar adenopathy measurable in only one dimension
- •Performance status - ECOG 0-1
- •Performance status - Karnofsky 70-100%
- •More than 6 months
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin normal
- •AST and ALT no greater than 1.5 times upper limit of normal (ULN) and alkaline phosphatase normal
- •AST and ALT normal and alkaline phosphatase no greater than 2.5 times ULN
- •Creatinine normal
- •Creatinine clearance at least 50 mL/min
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No history of cornea abnormalities (e.g., dry-eye syndrome, Sjögren's syndrome)
- •No congenital abnormality (e.g., Fuch's dystrophy)
- •No abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose)
- •No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)
- •No gastrointestinal tract disease resulting in the inability to take oral medications
- •No required IV alimentation
- •No peptic ulcer disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No history of allergy to compounds of similar chemical or biologic composition to erlotinib or other study agents
- •No significant traumatic injury within the past 21 days
- •No other uncontrolled concurrent illness
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No other active malignancy within the past 6 months except non-melanoma skin cancer
- 另有 12 项未显示
排除标准
- 未提供
研究组 & 干预措施
Group I (cisplatin, etoposide, erlotinib, and docetaxel)
Patients receive cisplatin IV over 2 hours on days 1, 8, 29, and 36; etoposide IV over 1 hour on days 1-5 and 29-33; and oral erlotinib once daily on days 1-49. Patients undergo concurrent radiotherapy 5 days a week for 7 weeks beginning on day 1. Patients receive consolidation therapy comprising docetaxel IV over 1 hour on days 50, 71, and 92. Some patients may also receive oral erlotinib once daily on days 50-112.
干预措施: cisplatin (Drug)
Group I (cisplatin, etoposide, erlotinib, and docetaxel)
Patients receive cisplatin IV over 2 hours on days 1, 8, 29, and 36; etoposide IV over 1 hour on days 1-5 and 29-33; and oral erlotinib once daily on days 1-49. Patients undergo concurrent radiotherapy 5 days a week for 7 weeks beginning on day 1. Patients receive consolidation therapy comprising docetaxel IV over 1 hour on days 50, 71, and 92. Some patients may also receive oral erlotinib once daily on days 50-112.
干预措施: etoposide (Drug)
Group I (cisplatin, etoposide, erlotinib, and docetaxel)
Patients receive cisplatin IV over 2 hours on days 1, 8, 29, and 36; etoposide IV over 1 hour on days 1-5 and 29-33; and oral erlotinib once daily on days 1-49. Patients undergo concurrent radiotherapy 5 days a week for 7 weeks beginning on day 1. Patients receive consolidation therapy comprising docetaxel IV over 1 hour on days 50, 71, and 92. Some patients may also receive oral erlotinib once daily on days 50-112.
干预措施: erlotinib hydrochloride (Drug)
Group I (cisplatin, etoposide, erlotinib, and docetaxel)
Patients receive cisplatin IV over 2 hours on days 1, 8, 29, and 36; etoposide IV over 1 hour on days 1-5 and 29-33; and oral erlotinib once daily on days 1-49. Patients undergo concurrent radiotherapy 5 days a week for 7 weeks beginning on day 1. Patients receive consolidation therapy comprising docetaxel IV over 1 hour on days 50, 71, and 92. Some patients may also receive oral erlotinib once daily on days 50-112.
干预措施: radiation therapy (Radiation)
Group I (cisplatin, etoposide, erlotinib, and docetaxel)
Patients receive cisplatin IV over 2 hours on days 1, 8, 29, and 36; etoposide IV over 1 hour on days 1-5 and 29-33; and oral erlotinib once daily on days 1-49. Patients undergo concurrent radiotherapy 5 days a week for 7 weeks beginning on day 1. Patients receive consolidation therapy comprising docetaxel IV over 1 hour on days 50, 71, and 92. Some patients may also receive oral erlotinib once daily on days 50-112.
干预措施: docetaxel (Drug)
Group I (cisplatin, etoposide, erlotinib, and docetaxel)
Patients receive cisplatin IV over 2 hours on days 1, 8, 29, and 36; etoposide IV over 1 hour on days 1-5 and 29-33; and oral erlotinib once daily on days 1-49. Patients undergo concurrent radiotherapy 5 days a week for 7 weeks beginning on day 1. Patients receive consolidation therapy comprising docetaxel IV over 1 hour on days 50, 71, and 92. Some patients may also receive oral erlotinib once daily on days 50-112.
干预措施: laboratory biomarker analysis (Other)
Group II (paclitaxel, carboplatin, and erlotinib
Patients receive induction chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21. Patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 43, 50, 57, 64, 71, 78, and 85 and oral erlotinib once daily on days 43-91. Patients undergo radiotherapy concurrently with consolidation therapy 5 days a week for 7 weeks beginning on day 43.
干预措施: erlotinib hydrochloride (Drug)
Group II (paclitaxel, carboplatin, and erlotinib
Patients receive induction chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21. Patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 43, 50, 57, 64, 71, 78, and 85 and oral erlotinib once daily on days 43-91. Patients undergo radiotherapy concurrently with consolidation therapy 5 days a week for 7 weeks beginning on day 43.
干预措施: radiation therapy (Radiation)
Group II (paclitaxel, carboplatin, and erlotinib
Patients receive induction chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21. Patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 43, 50, 57, 64, 71, 78, and 85 and oral erlotinib once daily on days 43-91. Patients undergo radiotherapy concurrently with consolidation therapy 5 days a week for 7 weeks beginning on day 43.
干预措施: paclitaxel (Drug)
Group II (paclitaxel, carboplatin, and erlotinib
Patients receive induction chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21. Patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 43, 50, 57, 64, 71, 78, and 85 and oral erlotinib once daily on days 43-91. Patients undergo radiotherapy concurrently with consolidation therapy 5 days a week for 7 weeks beginning on day 43.
干预措施: carboplatin (Drug)
Group II (paclitaxel, carboplatin, and erlotinib
Patients receive induction chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21. Patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 43, 50, 57, 64, 71, 78, and 85 and oral erlotinib once daily on days 43-91. Patients undergo radiotherapy concurrently with consolidation therapy 5 days a week for 7 weeks beginning on day 43.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
MTD defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity assessed using NCI CTCAE version 3.0
时间窗: 7 weeks
次要结局
- Response assessed using RECIST(Up to 8 weeks)
- Level of EGFR expression(Up to 8 weeks)