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: Randomizedphase 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.

Condition	Treatment or Intervention	Phase
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	Drug: carboplatin  Drug: cisplatin  Drug: efaproxiral  Drug: gemcitabine  Drug: paclitaxel  Drug: vinorelbine  Procedure: chemotherapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase III

Further Study Details: 

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).

• 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.
• 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Arizona
      St. Joseph's Hospital and Medical Center, Phoenix,  Arizona,  85013,  United States
Idaho
      North Idaho Cancer Center, Coeur D Alene,  Idaho,  83814,  United States
Kentucky
      Cancer Center at Lexington Clinic, Lexington,  Kentucky,  40504,  United States
Louisiana
      Willis - Knighton Cancer Center, Shreveport,  Louisiana,  71103-3951,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States
      St. Agnes Cancer Center, Baltimore,  Maryland,  21229,  United States
Washington
      Providence Everett Medical Center - Pacific Campus, Everett,  Washington,  98206,  United States
West Virginia
      Schiffler Cancer Center, Wheeling,  West Virginia,  26003,  United States
Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Ottawa Regional Cancer Centre, Ottawa,  Ontario,  K1H 1C4,  Canada
Canada, Quebec
      Centre Hospitalier Universitaire de Quebec, Quebec City,  Quebec,  G1R 2J6,  Canada
      CHUS-Hopital Fleurimont, Fleurimont,  Quebec,  J1H 5N4,  Canada
      Hopital Notre- Dame du CHUM, Montreal,  Quebec,  H2L 4M1,  Canada
      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada
Israel
      Rambam Medical Center, Haifa,  31096,  Israel
      Sheba Medical Center, Tel Hashomer,  52621,  Israel
      Soroka University Medical Center, Beer-Sheva,  84101,  Israel
      Tel-Aviv Sourasky Medical Center, Tel Aviv,  64239,  Israel

Study chairs or principal investigators

Hak Choy, MD,  Study Chair,  Simmons Cancer Center   

Study ID Numbers:  CDR0000271438; ALLOS-RSR13RT-013ELITE
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  March 6, 2003
ClinicalTrials.gov Identifier:  NCT00055887
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08