Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy and radiation therapy may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of radiation therapy when given with combination chemotherapy and to see how well they work in treating patients with non-small cell lung cancer that cannot be surgically removed.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of radiotherapy in combination with carboplatin and paclitaxel in patients with unresectable non-small cell lung cancer. Determine the 2-year survival of patients treated with this regimen. Determine the progression-free local control rate in patients treated this regimen. Determine the tolerability of this regimen in these patients. Assess the quality of life of patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of radiotherapy. Patients undergo radiotherapy* once daily 5 days a week for 7 weeks and 2 days (a total of 37 fractions). Patients concurrently receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes once weekly for 7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. NOTE: *No prophylactic nodal radiotherapy is administered Cohorts of 3-6 patients receive escalating doses of radiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 12 additional patients are treated at that dose level in the phase II portion of the study. Beginning 3 weeks after completion of radiotherapy, patients receive paclitaxel and carboplatin as above. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, once during the last week of radiotherapy, and then every 3 months for 2 years. Patients are followed at 3 weeks, every 3 months for 21 months, and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.

Official Title
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Phase I/II Study Of Concurrent Chemotherapy And Escalating Doses Of Radiotherapy (RT) For Unresectable Non-Small Cell Lung Cancer (NSCLC) Using A New RT Paradigm

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: paclitaxel
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) Stage I, II, or III NSCLC that is unresectable due to tumor extent or other medical reasons Measurable disease Tumor must not exceed volume that would require radiation volumes greater than those allowed on this study No more than blunting of the costophrenic angle on chest x-ray due to pleural effusions No more than small effusions seen on chest CT scan only No supraclavicular adenopathy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Total bilirubin no greater than 1.5 times upper limit of normal (ULN) OR Direct bilirubin no greater than 1.5 times ULN AST no greater than 3 times ULN Renal: Creatinine clearance at least 40 mL/min Cardiovascular: No New York Heart Association class III or IV heart disease Pulmonary: FEV_1 at least 1 L or 35% of predicted Other: No grade 2 or greater peripheral neuropathy No weight loss of 10% or more within the past 3 months No uncontrolled infection No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinoma (carcinoma in situ), or localized prostate cancer No other severe underlying disease that would preclude study participation Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic: No prior biologic therapy for NSCLC No concurrent biologic therapy No concurrent prophylactic filgrastim (G-CSF) Chemotherapy: No prior chemotherapy for NSCLC No other concurrent chemotherapy Endocrine therapy: No prior endocrine therapy for NSCLC Radiotherapy: No prior radiotherapy for NSCLC Surgery: No prior surgery for NSCLC

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: radiotherapy + paclitaxel + carboplatin<br>Patients undergo radiotherapy once daily 5 days a week for 7 weeks and 2 days (a total of 37 fractions). Patients concurrently receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes once weekly for 7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 3 weeks after completion of radiotherapy, patients receive paclitaxel and carboplatin as above. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, once during the last week of radiotherapy, and then every 3 months for 2 years. Patients are followed at 3 weeks, every 3 months for 21 months, and then every 6 months for 3 years. | Drug: carboplatin<br> <br> Drug: paclitaxel<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) as assessed by dose-limiting toxicity within 1 month after completion of study treatment (phase I) |  | Up to 1 month | 
| Survival at 2 years (phase II) |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival time |  | Up to 5 years | 
| Toxicity |  | Up to 5 years | 
| Time to progression |  | Up to 5 years | 
| Time to local progression |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I non-small cell lung cancer, stage II non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer