Phase II Study of Sequential Dose-Dense Chemotherapy and Dose-Intense Erlotinib for the Initial Treatment of Advanced Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Time to Progression
研究概览
简要总结
This phase II trial is studying how well docetaxel given together with cisplatin and pegfilgrastim followed by erlotinib hydrochloride works in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving dose-dense combination chemotherapy together with pegfilgrastim and erlotinib hydrochloride may kill more tumor cells
详细描述
PRIMARY OBJECTIVES:
I. To determine if this regimen improves the time-to-progression for patients with advanced non-small cell lung cancer (NSCLC) compared to historical controls.
SECONDARY OBJECTIVES:
I. To assess response rate and median survival. II. To evaluate tumor biomarkers that could predict response and survival for patients treated with this regimen including endothelial growth factor receptor (EGFR) expression, EGFR Fluorescence in situ hybridization (FISH), and k-ras mutations.
III. To evaluate genetic polymorphisms as markers of response and survival for patients treated with this regimen including polymorphisms in XPD, XRCC1, XRCC3, and cyclin D1.
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
- •Histologic Documentation: Either histologic or cytologic documentation of non-small cell carcinoma (NSCLC) is necessary, and the following diagnostic categories are acceptable: squamous carcinoma, basaloid carcinoma, adenocarcinoma, bronchioloalveolar carcinoma, adenosquamous carcinoma, large cell carcinoma (not neuroendocrine), sarcomatoid carcinoma, and non-small cell carcinoma not otherwise specified (NOS); histologic or cytologic documentation of recurrence is required in patients who were previously completely resected
- •Advanced Disease: Stage IIIB because of malignant pleural or pericardial effusion or stage IV disease
- •Patients must be ineligible for Avastin or decline treatment with Avastin
- •Prior Treatment: No prior chemotherapy or treatment with an EGFR inhibitor is allowed; brain metastasis must be under control (patient neurologically stable)
- •All Patients must have Measurable or Non-Measurable Disease: measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension; the longest diameter of measurable lesions must be >= 20 mm with conventional techniques or >= 10 mm with spiral computed tomography (CT) scan; non-measurable disease includes the following:
- •Bone lesions
- •Brain metastasis or leptomeningeal disease
- •Pleural/pericardial effusion
- •Abdominal masses that are not confirmed and followed by imaging techniques
- •Cystic lesions
- •Tumor lesions situated in a previously irradiated area
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- •Granulocytes >= 1,500/ul
- •Platelets >= 100,000/ul
- •Creatinine =< upper limit of normal (ULN)
- •Bilirubin =< 1.5 mg/dl
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 1.5 x ULN
- •Alkaline (Alk.) phosphatase (phos.) =< 2.5 x ULN
- •Patients must provide verbal and written informed consent to participate in the study
排除标准
- •Patients who are pregnant or nursing because of significant risk to the fetus/infant
- •Patients with neuropathy >= grade 2
- •Patients with a psychiatric illness which would prevent the patient from giving informed consent
- •Patients who are unable to take oral medications
- •Women with child-bearing potential or men who are sexual partners of women with child-bearing potential who are not willing to practice adequate contraceptive measures
研究组 & 干预措施
Treatment (chemo, chemoprotection, antiangiogenesis therapy)
Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
干预措施: cisplatin (Drug)
Treatment (chemo, chemoprotection, antiangiogenesis therapy)
Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
干预措施: pegfilgrastim (Biological)
Treatment (chemo, chemoprotection, antiangiogenesis therapy)
Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
干预措施: erlotinib hydrochloride (Drug)
Treatment (chemo, chemoprotection, antiangiogenesis therapy)
Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (chemo, chemoprotection, antiangiogenesis therapy)
Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
干预措施: polymorphism analysis (Genetic)
Treatment (chemo, chemoprotection, antiangiogenesis therapy)
Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacogenomic studies (Other)
Treatment (chemo, chemoprotection, antiangiogenesis therapy)
Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
干预措施: genetic linkage analysis (Genetic)
Treatment (chemo, chemoprotection, antiangiogenesis therapy)
Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
干预措施: docetaxel (Drug)
结局指标
主要结局
Time to Progression
时间窗: 2 years
Determined using RECIST. Estimated using the Kaplan-Meier method. Log-rank tests will be used to test for differences and Cox proportional hazards regression modeling will be used to adjust for patient demographics and characteristics such as smoking status at baseline (actively/non-actively smoking). Progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
次要结局
- Median Survival Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood(2 years)
- Response Rate Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood(2 years)