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)
Overview
- Phase
- Phase 3
- Intervention
- carboplatin
- Conditions
- Lung Cancer
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 589
- Locations
- 233
- Primary Endpoint
- Overall Survival Time
- Status
- Terminated
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
Detailed Description
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. OUTLINE: This is a randomized study. Patients are stratified according to disease histology (squamous vs nonsquamous), performance status (0 vs 1), disease stage (IIIA vs IIIB), and time of randomization (before addition of chemoradiotherapy vs after). Patients are randomized to one of two treatment arms. ARM A: Patients receive paclitaxel intravenously (IV) over 3 hours immediately followed by carboplatin IV over 15-30 minutes on days 1 and 22. Treatment continues every 22 days in the absence of unacceptable toxicity or disease progression. ARM B: Patients receive paclitaxel and carboplatin as in arm A. Patients also receive oral thalidomide and oral low-dose aspirin daily beginning on day 1 for up to 24 months in the absence of disease progression. Beginning between days 43-50, patients in both arms with stable or responding disease receive chemoradiotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 15-30 minutes once weekly for 6 weeks and radiotherapy (RT) 5 days a week for 6 weeks. Arm B patients continue oral thalidomide. Patients are followed every 2 months for 2 years and then every 6 months for 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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
Intervention: carboplatin
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
Intervention: paclitaxel
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
Intervention: radiation therapy
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.
Intervention: carboplatin
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.
Intervention: paclitaxel
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.
Intervention: thalidomide
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.
Intervention: radiation therapy
Outcomes
Primary Outcomes
Overall Survival Time
Time Frame: 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
Secondary Outcomes
- 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)