A Randomized Phase III Trial of Carboplatin, Paclitaxel and Thoracic Radiotherapy, With or Without Thalidomide, in Patients With Stage III Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 589
- 试验地点
- 233
- 主要终点
- Overall Survival Time
研究概览
简要总结
This randomized phase III trial is studying carboplatin, paclitaxel, radiation therapy, and thalidomide to see how well they work compared to carboplatin, paclitaxel, and radiation therapy alone in treating patients with newly diagnosed stage III non-small cell lung cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of non-small cell lung cancer by stopping blood flow to the tumor. It is not yet known if combination chemotherapy plus radiation therapy is more effective with or without thalidomide.
详细描述
OBJECTIVES:
I. Compare the survival and time to progression of patients with stage IIIA or IIIB non-small cell lung cancer when treated with carboplatin, paclitaxel, and chemoradiotherapy with or without thalidomide.
II. Evaluate the toxicity of the thalidomide-containing regimen and compare response rates of the two groups.
III. Determine whether the inactivation of p16, Death-associated protein kinase (DAP-kinase), O6-methylguanine-DNA methyltransferase (MGMT) gene, or tissue-inhibitor of metalloproteinase 3 (TIMP-3) genes can be used to predict survival in these patients treated with this regimen.
IV. Determine whether the detection of a methylation biomarker in serum can be used to predict survival in these patients treated with this regimen.
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
- •Histologically confirmed newly diagnosed non-small cell bronchogenic carcinoma
- •Squamous cell
- •Adenocarcinoma
- •Large cell undifferentiated
- •Bronchoalveolar
- •Non-small cell carcinoma not otherwise stated
- •Unresectable stage IIIA
- •Mediastinal lymph node enlargement of at least 1 cm but less than 2 cm on computed tomography (CT) scans must have mediastinotomy or thoracoscopy to rule out resectability
- •Stage IIIB disease without significant pleural effusion
- •Seen on CT scan only (not seen on chest x-ray) or does not reaccumulate after 1 thoracentesis and is cytologically negative
- •Metastases to contralateral, mediastinal, or supraclavicular nodes allowed
- •Bidimensionally measurable or evaluable disease
- •18 and over
- •ECOG performance status 0-1
- •Adequate hematopoietic, hepatic, and renal function obtained <=4 weeks prior to registration:
- •Platelet count at least 100,000/mm^3
- •White Blood Cell (WBC) count at least 4,000/mm^3 OR absolute neutrophil count at least 2,000/mm^3
- •Bilirubin normal
- •Serum glutamic oxaloacetic transaminase (SGOT) no greater than 2.5 times upper limit of normal
- •Creatinine no greater than 1.5 mg/dL OR creatinine clearance at least 60 mL/min
- •Fertile patients must use 2 methods of effective contraception for 4 weeks prior to, during, and for 4 weeks after study therapy
- •Concurrent filgrastim (G-CSF) allowed for persistent neutropenia
排除标准
- •Positive pregnancy test,pregnant or nursing
- •Uncontrolled high blood pressure, unstable angina, congestive heart failure, or myocardial infarction within the prior year
- •Serious cardiac arrhythmias requiring medication
- •Prior radiotherapy to only area of measurable or active tumor
- •Less than 5 years since prior chemotherapy
- •Other active malignancies
- •Serious uncontrolled active infection
- •Evidence of greater than grade 1 neuropathy by history or physical examination
- •History of seizure disorders
- •Contraindication to daily low-dose (81 mg/day) aspirin
研究组 & 干预措施
Arm A (Paclitaxel + Carboplatin + RT)
Induction chemotherapy dosing: Paclitaxel, 225 mg/m² (3 hour infusion) Day 1. Carboplatin, area under the plasma drug concentration versus time curve (AUC) =6.0, 15-30 min IV infusion immediately following paclitaxel, Day 1
Concurrent chemotherapy / radiotherapy dosing: Paclitaxel, 45 mg/m2, administered weekly during radiotherapy over one hour. Carboplatin, AUC=2, 15- 30 minutes IV infusion immediately following paclitaxel; administered weekly during radiotherapy
Radiation therapy started between days 43-50 from day 1 of cycle 1. The primary tumor and areas of known nodal disease received 60 Gy at 2.0 Gy fractions, 5 fractions/week for 30 fractions over 6 weeks to the post chemotherapy tumor volume as seen on computed tomography (CT). The initial 50 Gy was delivered to target volume (TV). The final 10 Gy was delivered to a reduced volume targeting defined by TV
干预措施: carboplatin (Drug)
Arm A (Paclitaxel + Carboplatin + RT)
Induction chemotherapy dosing: Paclitaxel, 225 mg/m² (3 hour infusion) Day 1. Carboplatin, area under the plasma drug concentration versus time curve (AUC) =6.0, 15-30 min IV infusion immediately following paclitaxel, Day 1
Concurrent chemotherapy / radiotherapy dosing: Paclitaxel, 45 mg/m2, administered weekly during radiotherapy over one hour. Carboplatin, AUC=2, 15- 30 minutes IV infusion immediately following paclitaxel; administered weekly during radiotherapy
Radiation therapy started between days 43-50 from day 1 of cycle 1. The primary tumor and areas of known nodal disease received 60 Gy at 2.0 Gy fractions, 5 fractions/week for 30 fractions over 6 weeks to the post chemotherapy tumor volume as seen on computed tomography (CT). The initial 50 Gy was delivered to target volume (TV). The final 10 Gy was delivered to a reduced volume targeting defined by TV
干预措施: paclitaxel (Drug)
Arm A (Paclitaxel + Carboplatin + RT)
Induction chemotherapy dosing: Paclitaxel, 225 mg/m² (3 hour infusion) Day 1. Carboplatin, area under the plasma drug concentration versus time curve (AUC) =6.0, 15-30 min IV infusion immediately following paclitaxel, Day 1
Concurrent chemotherapy / radiotherapy dosing: Paclitaxel, 45 mg/m2, administered weekly during radiotherapy over one hour. Carboplatin, AUC=2, 15- 30 minutes IV infusion immediately following paclitaxel; administered weekly during radiotherapy
Radiation therapy started between days 43-50 from day 1 of cycle 1. The primary tumor and areas of known nodal disease received 60 Gy at 2.0 Gy fractions, 5 fractions/week for 30 fractions over 6 weeks to the post chemotherapy tumor volume as seen on computed tomography (CT). The initial 50 Gy was delivered to target volume (TV). The final 10 Gy was delivered to a reduced volume targeting defined by TV
干预措施: radiation therapy (Radiation)
Arm B (Paclitaxel + Carboplatin + RT+ Thalidomide)
paclitaxel, carboplatin, and radiotherapy are same as those in Arm A.
thalidomide: Induction chemotherapy dosing, oral daily, starting Day 1 for 24 months or until disease progression. Concurrent chemotherapy / radiotherapy dosing, oral daily, begin with 200 mg thalidomide as a single dose at bedtime. The dose is then increased by 100 mg every week as tolerated up to a total dose of 1000 mg.
干预措施: carboplatin (Drug)
Arm B (Paclitaxel + Carboplatin + RT+ Thalidomide)
paclitaxel, carboplatin, and radiotherapy are same as those in Arm A.
thalidomide: Induction chemotherapy dosing, oral daily, starting Day 1 for 24 months or until disease progression. Concurrent chemotherapy / radiotherapy dosing, oral daily, begin with 200 mg thalidomide as a single dose at bedtime. The dose is then increased by 100 mg every week as tolerated up to a total dose of 1000 mg.
干预措施: paclitaxel (Drug)
Arm B (Paclitaxel + Carboplatin + RT+ Thalidomide)
paclitaxel, carboplatin, and radiotherapy are same as those in Arm A.
thalidomide: Induction chemotherapy dosing, oral daily, starting Day 1 for 24 months or until disease progression. Concurrent chemotherapy / radiotherapy dosing, oral daily, begin with 200 mg thalidomide as a single dose at bedtime. The dose is then increased by 100 mg every week as tolerated up to a total dose of 1000 mg.
干预措施: thalidomide (Drug)
Arm B (Paclitaxel + Carboplatin + RT+ Thalidomide)
paclitaxel, carboplatin, and radiotherapy are same as those in Arm A.
thalidomide: Induction chemotherapy dosing, oral daily, starting Day 1 for 24 months or until disease progression. Concurrent chemotherapy / radiotherapy dosing, oral daily, begin with 200 mg thalidomide as a single dose at bedtime. The dose is then increased by 100 mg every week as tolerated up to a total dose of 1000 mg.
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Overall Survival Time
时间窗: every other month until 24 months from study entry, then every 3 months for year 3, every 4 months for year 4 and every 6 months for year 5
Survival time is defined as time from study entry to death from any cause
次要结局
- Time to Disease Progression(every other month until 24 months from study entry, every 3 months for year 3, every 4 months for the 4th year and every 6 months for the 5th year)
- Response Rate at Best Response to Treatment(every other month until 24 months from study entry, every 3 months for year 3, every 4 months for the 4th year and every 6 months for the 5th year)