Gemcitabine, Carboplatin or Paclitaxel Plus Radiation Therapy in Treating Patients With Stage IIIA or IIIB Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine, carboplatin, and paclitaxel, work in 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 radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining combination chemotherapy with radiation therapy in treating patients who have stage IIIA or stage IIIB non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose (MTD) of gemcitabine when administered with carboplatin and thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in patients with stage IIIA or IIIB non-small cell lung cancer. Determine the MTD of gemcitabine and paclitaxel when administered with thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in these patients. OUTLINE: This is a multicenter, dose-escalation study of gemcitabine and paclitaxel. Patients are sequentially assigned to 1 of 3 treatment regimens. Regimen A: Patients receive gemcitabine IV over 30-60 minutes on days 1, 8, 22, 29, and 43 and thoracic radiotherapy daily 5 days a week for 7 weeks beginning on day 1. Regimen B (closed to accrual as of 5/13/03): Patients receive gemcitabine and thoracic radiotherapy as in regimen A and carboplatin IV over 30 minutes on days 1, 8, 22, 29, and 43. Regimen C: Patients receive gemcitabine and thoracic radiotherapy as in regimen A and paclitaxel IV over 1 hour on days 1, 8, 22, 29, and 43. At 3 weeks after completion of chemoradiotherapy, all patients receive adjuvant gemcitabine IV over 30-60 minutes on days 71, 78, 92, and 99 and carboplatin IV over 30 minutes on days 71 and 92. The first 6 patients enrolled receive regimen A to determine the safety of the initial dose of gemcitabine. After completion of regimen A, cohorts of 3-6 patients receive escalating doses of gemcitabine in regimen B (closed to accrual as of 5/13/03) until the maximum tolerated dose (MTD) is determined. In a separate sequence, cohorts of 3-6 patients receive alternating escalating doses of gemcitabine and paclitaxel in regimen C until the MTD is determined. The MTD is defined as the dose preceding that at which at least 3 of 6 patients experience dose-limiting toxicity. Patients are followed at 3 months, 6 months, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A maximum of 78 patients will be accrued for this study within 29 months.

Official Title
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A Phase I Study of Gemcitabine, Carboplatin or Gemcitabine, Paclitaxel and Radiation Therapy Followed by Adjuvant Chemotherapy for Patients With Favorable Prognosis Inoperable Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed loco-regionally advanced non-small cell lung cancer meeting one of the following staging criteria: Medically inoperable stage IIIA Unresectable stage IIIA or IIIB Measurable disease on three-dimensional planning CT scan No post-resection intrathoracic tumor recurrence No pleural effusion on chest x-ray except those occurring after attempted thoracotomy or other invasive thoracic procedure No evidence of small cell histology No evidence of hematogenous or distant metastases PATIENT CHARACTERISTICS: Age: Not specified Performance status: Zubrod 0-1 Life expectancy: Not specified Hematopoietic: Platelet count at least 100,000/mm^3 Absolute granulocyte count at least 2,000/mm^3 Hemoglobin at least 8.0 g/dL Hepatic: Bilirubin no greater than 1.5 mg/dL Serum glutamate oxaloacetate transaminase (SGOT) no greater than 1.5 times upper limit of normal (unless caused by documented benign disease) Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: No myocardial infarction within the past 6 months No symptomatic heart disease, including angina, congestive heart failure, or uncontrolled arrhythmia Pulmonary: Forced expiratory volume (FEV)_1 greater than 1,000 mL Other: No other invasive malignancy within the past 3 years except nonmelanoma skin cancer No weight loss of more than 10% in 3 months prior to diagnosis Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior thoracic or neck radiotherapy Surgery: See Disease Characteristics No prior complete or subtotal tumor resection
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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Sequence A: Gemcitabine 300 mg/m2/week plus radiation therapy (RT) | Drug: gemcitabine hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 2<br>Sequence B: Gemcitabine 300 mg/m2/week plus paclitaxel 30 mg/m2/week and RT | Drug: gemcitabine hydrochloride<br> <br> Drug: paclitaxel<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 3<br>Sequence A: Gemcitabine 300 mg/m2/week plus carboplatin 2 AUC and RT | Drug: carboplatin<br> <br> Drug: gemcitabine hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 4<br>Sequence B: Gemcitabine 450 mg/m2/week plus paclitaxel 30 mg/m2/week and RT | Drug: gemcitabine hydrochloride<br> <br> Drug: paclitaxel<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 6<br>Sequence B: Gemcitabine 450 mg/m2/week plus paclitaxel 40 mg/m2/week and RT | Drug: gemcitabine hydrochloride<br> <br> Drug: paclitaxel<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 8<br>Sequence B: Gemcitabine 600 mg/m2/week plus paclitaxel 40 mg/m2/week and RT | Drug: gemcitabine hydrochloride<br> <br> Drug: paclitaxel<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 10<br>Sequence B: Gemcitabine 600 mg/m2/week plus paclitaxel 50 mg/m2/week and RT | Drug: gemcitabine hydrochloride<br> <br> Drug: paclitaxel<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 12<br>Sequence B: Gemcitabine 750 mg/m2/week plus paclitaxel 50 mg/m2/week and RT | Drug: gemcitabine hydrochloride<br> <br> Drug: paclitaxel<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 14<br>Sequence B: Gemcitabine 900 mg/m2/week plus paclitaxel 50 mg/m2/week and RT | Drug: gemcitabine hydrochloride<br> <br> Drug: paclitaxel<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 5<br>Sequence A: Gemcitabine 450 mg/m2/week plus carboplatin 2 AUC and RT | Drug: carboplatin<br> <br> Drug: gemcitabine hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 7<br>Sequence A: Gemcitabine 600 mg/m2/week plus carboplatin 2 AUC and RT | Drug: carboplatin<br> <br> Drug: gemcitabine hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 9<br>Sequence A: Gemcitabine 750 mg/m2/week plus carboplatin 2 AUC and RT | Drug: carboplatin<br> <br> Drug: gemcitabine hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Arm 11<br>Sequence A: Gemcitabine 900 mg/m2/week plus carboplatin 2 AUC and RT | Drug: carboplatin<br> <br> Drug: gemcitabine hydrochloride<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 |
| --- | --- | --- |
| To determine the maximum tolerated dose of gemcitabine with carboplatin-based chemotherapy and radiation therapy |  | From start of treatment to 90 days | 
| To determine the maximum tolerated dose of gemcitabine with paclitaxel-based chemotherapy and radiation therapy |  | From start of treatment to 90 days | 

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