Gemcitabine Plus Radiation Therapy or Combination Chemotherapy 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 radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase I/II trial to compare the effectiveness of gemcitabine with radiation therapy alone or following two-drug combination chemotherapy in treating patients with stage III non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of twice-weekly gemcitabine when delivered concurrently with thoracic radiotherapy alone or following 2 cycles of induction chemotherapy in patients with Stage IIIA or IIIB non-small cell lung cancer. Assess the toxicity of concurrent thoracic radiation and gemcitabine in these patients. Determine the effectiveness of concurrent radiation and gemcitabine by determining the complete response rate, partial response rate, time to recurrence, pattern of recurrence, and overall survival in a cohort of these patients. OUTLINE: This is an alternating two arm, dose escalation, multicenter study. Arm I: Patients receive twice-weekly gemcitabine as a 30 minute infusion. Concurrent radiation therapy is administered 5 days a week for 6 weeks. Arm II: Patients receive 2 cycles of induction chemotherapy consisting of gemcitabine as a 30 minute infusion on day 1 and 8 and cisplatin IV over 1 hour on day 1. Each cycle is 21 days. Patients then receive gemcitabine and radiation therapy as in arm I. Cohorts of 3 patients are enrolled into each treatment arm at each dose level of gemcitabine. Toxicity for each arm is assessed independently. Once dose limiting toxicity (DLT) is observed at any dose level, 3 more patients are enrolled at the same dose level. The maximum tolerated dose (MTD) is defined as the dose at which no more than 1 of 6 patients experiences grade 4 toxicity, or no more than 4 of 6 patients experience grade 3 or worse toxicity (DLT). After the MTD is determined for each treatment arm, additional patients are treated at that dose level for the phase II portion of the study. Patients are followed every 3 months for 2 years, then every 4 months for the next 2 years, and then every 6 months thereafter. PROJECTED ACCRUAL: There will be approximately 24-48 patients accrued into this study within 1-2 years.

Official Title
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Alternating Phase I/II Trials of Twice-Weekly Infusion Gemcitabine (2'2'-Difluoro-2'-Deoxycytidine) and Concurrent Thoracic Radiation Alone - Or Following 2 Cycles of Cisplatin/Gemcitabine Induction Chemotherapy for the Treatment of Stage IIIA/IIIB Non Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: gemcitabine hydrochloride
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage IIIA or IIIB non-small cell lung cancer that is unicentric and inoperable, including the following cellular types: Squamous cell carcinoma Adenocarcinoma Bronchoalveolar carcinoma Large cell anaplastic carcinoma Non-small cell lung cancer not otherwise specified Tumors may be multifocal if all of disease is believed to be result of direct spread Disease must be fully accessible by radiotherapy ports for the entire prescribed dose No supraclavicular nodes or diffuse pleural involvement No contralateral hilar disease or an exudative, bloody, or cytologically malignant effusion Measurable disease required for phase II of this study PATIENT CHARACTERISTICS: Age: Any age Performance status: ECOG 0-2 Life expectancy: At least 1 year Hematopoietic: Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin greater than 10 g/dL Hepatic: Bilirubin no greater than 2.0 mg/dL Renal: BUN no greater than 1.5 times normal Creatinine no greater than 1.5 times normal Pulmonary: FEV1 no greater than 1 liter except if tumor has negatively impacted pulmonary function Other: No other serious medical or psychiatric illness No prior lung cancer except if free of disease for more than 3 years No other prior malignancy except nonmelanoma skin cancer or if free of disease for more than 1 year Not pregnant or nursing Negative pregnancy test PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior thoracic radiotherapy Concurrent radiotherapy to other anatomic sites allowed Surgery: Not specified

Ages Eligible for Study
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Maximum Age: 120 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: gemcitabine hydrochloride|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| •Determine the maximum tolerated dose of twice-weekly gemcitabine when delivered concurrently with thoracic radiotherapy |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assess the efficacy of dose of twice-weekly gemcitabine when delivered concurrently with thoracic radiotherapy |  | 72 days | 

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