Chemotherapy and Radiation Therapy With or Without Efaproxiral in Treating Patients With Stage III 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. Drugs such as efaproxiral may make the tumor cells more sensitive to radiation therapy. It is not yet known if chemotherapy combined with radiation therapy is more effective with or without efaproxiral in treating non-small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy combined with radiation therapy with or without efaproxiral in treating patients who have stage III non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Compare the overall survival of patients with stage IIIA or IIIB non-small cell lung cancer treated with induction chemotherapy followed by radiotherapy with or without efaproxiral. Compare time to progression, response rate, and pattern of failure of patients treated with these regimens. Determine the safety of efaproxiral in these patients. Determine the pharmacokinetics of efaproxiral in these patients. Compare quality of life of patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to chemotherapy regimen, Karnofsky performance status (70-80% vs 90-100%), and disease stage (IIIA vs IIIB). Induction therapy phase: Patients receive 1 of the following induction chemotherapy regimens: Paclitaxel and carboplatin: Patients receive paclitaxel IV and carboplatin IV on day 1. Treatment repeats every 21 days for a total of 2 courses. Cisplatin and gemcitabine: Patients receive cisplatin IV on day 2 and gemcitabine IV on days 1, 8, and 15. Treatment repeats every 28 days for a total of 2 courses. Cisplatin and vinorelbine: Patients receive cisplatin IV on day 1 and vinorelbine IV on days 1, 8, and either 15 or 22. Treatment repeats every 28 days for a total of 2 courses. Randomized phase: Within 42 days after completion of chemotherapy, patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive efaproxiral IV over 30-45 minutes with supplemental oxygen and then undergo concurrent radiotherapy 5 days a week for 7 weeks. Arm II: Patients receive supplemental oxygen and undergo radiotherapy as in arm I. Quality of life is assessed at baseline, on days 1 and 16 of radiotherapy, monthly for 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. Patients are followed monthly for 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 659 patients will be accrued for this study.

Official Title
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A Phase III Randomized, Open-Label Comparative Study of Induction Chemotherapy Followed by Thoracic Radiation Therapy With Supplemental Oxygen, With or Without Concurrent RSR13 (Efaproxiral), in Patients With Locally Advanced Unresectable (Stage IIIA/IIIB) Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: cisplatin
* Drug: efaproxiral
* Drug: gemcitabine hydrochloride
* Drug: paclitaxel
* Drug: vinorelbine ditartrate
* Procedure: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed locally advanced, unresectable non-small cell lung cancer of 1 of the following subtypes: Adenocarcinoma Squamous cell carcinoma Large cell carcinoma Poorly differentiated carcinoma Stage IIIA or IIIB T1 or T2, N2 T3, N1 or N2 T4, any N Any T, N3 Histological or cytological confirmation of at least 1 positive lymph node required if the largest mediastinal node that is the basis of stage III disease is less than 2.0 cm in diameter Clinically or radiologically measurable disease of at least 2.0 cm Partially resected stage IIIB disease allowed provided a measurable lesion remains No pleural effusion that is bloody, cytologically positive, or re-accumulated after thoracentesis No metastatic disease by CT scan or MRI PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 70-100% Life expectancy Not specified Hematopoietic Hemoglobin at least 10 g/dL WBC at least 3,000/mm^3 Absolute granulocyte count at least 2,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST and ALT no greater than 2.5 times ULN Renal Creatinine no greater than 1.5 mg/dL Cardiovascular No clinically active congestive heart failure No unstable angina No severe arrhythmia by ECG Pulmonary FVC and FEV_1 at least 50% of normal Resting oxygen saturation by pulse oximetry (SpO_2) at least 90% on room air Exercise SpO_2 at least 90% on room air Other Not pregnant or nursing Negative pregnancy test Fertile female patients must use effective contraception during and for 30 days after study therapy Male patients must use effective contraception during and for 90 days after study therapy No loss of more than 10% of body weight within the past 3 months No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No significantly altered mental status or dementia that would preclude giving informed consent No active infection No other serious underlying medical condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy More than 28 days since prior biologic therapy No concurrent colony-stimulating factors (randomized phase only) No biologic therapy during and for 1 month after study therapy No immune response modifiers during and for 1 month after study therapy Chemotherapy No prior systemic chemotherapy Endocrine therapy No hormonal therapy during and for 1 month after study therapy Radiotherapy No prior thoracic radiotherapy Surgery See Disease Characteristics No prior total surgical resection Other More than 28 days since prior investigational drugs or devices No prior efaproxiral No other cytotoxic therapy during and for 1 month after study therapy

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
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carboplatin|nan|
|Drug: cisplatin|nan|
|Drug: efaproxiral|nan|
|Drug: gemcitabine hydrochloride|nan|
|Drug: paclitaxel|nan|
|Drug: vinorelbine ditartrate|nan|
|Procedure: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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