Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

Inclusion Criteria:

• Histologically or cytologically confirmed single, primary, bronchogenic, non-small cell lung cancer (NSCLC)

  • Newly diagnosed disease
  • Unresectable disease
  • No more than 1 parenchymal lesions on same or opposite sides of the lungs

• Meets 1 of the following stage criteria:

  • Stage IIIA (N2) disease meeting the following criteria:

    • N2 mediastinal lymph nodes must be multiple and/or bulky on CT scan or x-ray so that the patient is not a candidate for induction chemotherapy or chemoradiotherapy followed by surgical resection

    • N2 status must be documented by ≥ 1 of the following methods:

      • Histologically or cytologically confirmed N2 disease by exploratory thoracotomy, thoracoscopy, mediastinoscopy, mediastinotomy, Chamberlain procedure, Wang needle biopsy (WNB), fine needle aspiration (FNA) under bronchoscopic or CT guidance, or any other method
      • Node positive by fludeoxyglucose-positron emission tomography (FDG-PET) scan
      • Nodes > 3 cm on CT scan
      • Paralyzed left true vocal cord with separate left lung primary distinct from anterior-posterior window nodes on CT scan

  • Stage IIIB disease meeting ≥ 1 of the following criteria:

    • Histologically or radiographically confirmed positive N3 nodes*, documented by ≥ 1 of the following methods:

      • FNA, core needle biopsy (CNB), or excisional biopsy of supraclavicular N3 nodes
      • Biopsy of contralateral mediastinal N3 nodes by mediastinoscopy, mediastinotomy, or thoracotomy
      • FNA, CNB, or WNB under CT or bronchoscopic fluoroscopic guidance of enlarged contralateral N3 mediastinal nodes
      • Contralateral mediastinal nodes > 3 cm on CT scan
      • Node positivity by FDG-PET scan
      • Right-sided primary with paralyzed left true vocal cord

    • T4 lesions of any size that invade the mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina, documented by ≥ 1 of the following methods:

      • Written documentation of type of T4 extent if patient had a prior exploratory thoracotomy or thoracoscopy
      • T4 involvement of the trachea or carina by direct bronchoscopic visualization
      • T4 involvement of the heart, esophagus, aorta, or vertebral body by CT scan, MRI, or transesophageal ultrasound
      • T4 involvement of the mediastinum by CT scan or MRI if, in the absence of the above organ involvement, there is soft tissue extension directly into the mediastinal space**

• Meets 1 of the following risk criteria:

  • Low risk disease, meeting the following criteria:

    • Non-squamous cell NSCLC, including adenocarcinoma, bronchoalveolar cell carcinoma, or large cell carcinoma

      • If mixed histology, the squamous cell carcinoma component must be < 50%
      • Histology or cytology from involved mediastinal or supraclavicular lymph nodes allowed if a separate distal primary lesion is clearly evident on radiographs (i.e., second biopsy not required)
    • No primary tumor with cavitation and/or tumor within 1 cm of a major vessel
    • No hemoptysis (i.e., bright red blood ≥ ½ teaspoon) in the past 28 days

  • High-risk* disease, meeting ≥ 1 of the following criteria:

    • Squamous cell NSCLC

      • If mixed histology, the squamous cell component must be ≥ 50%

    • Tumor with any histology that has cavitation or is located within 1 cm of a major vessel

      • No aortic involvement
    • Any histology and hemoptysis (i.e., bright red blood ≥ ½ teaspoon) within past 28 days

• Measurable or nonmeasurable disease by CT scan or MRI

  • Pleural effusions, ascites, and laboratory parameters are not acceptable as the only evidence of disease
• No pleural effusion except for small pleural effusion visible on CT scan or MRI alone
• No pericardial effusions
• No metastatic disease involving the contralateral chest, liver, or adrenals confirmed by CT scan of the upper abdomen or by chest CT scan with complete liver and adrenals in the report
• Patients must be offered participation in SWOG-S9925 (Lung Cancer Specimen Repository Protocol)
• No brain metastases by CT scan or MRI
• No evidence of cavitation
• Creatinine normal
• Creatinine clearance ≥ 50 mL/min
• FEV_1 ≥ 2.0 liters OR predicted FEV_1 of the contralateral lung > 800 mL
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Urine protein: creatinine ratio ≤ 0.5 by urinalysis OR urine protein < 1,000 mg by 24-hour urine collection
• INR < 1.5
• Zubrod performance status 0-1
• No sensory neuropathy > grade 1
• No cerebrovascular accident within the past 6 months
• No myocardial infarction or unstable angina within the past 6 months
• No uncontrolled hypertension
• No New York Heart Association class II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No clinically significant peripheral vascular disease
• No evidence of bleeding diathesis or coagulopathy
• No pathologic condition other than lung cancer that carries a high risk of bleeding
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No serious, nonhealing wound, ulcer, or bone fracture
• No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer for which the patient is currently in complete remission, or other cancer for which the patient has been disease-free for 5 years

• Not pregnant or nursing

  • No nursing during and for ≥ 6 months after the last dose of bevacizumab
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after the last dose of bevacizumab
• Must have pre-treatment simulation demonstrating a V20 ≤ 35% with planned radiation dose of 6,480 cGy

• No prior surgical resection

  • Prior exploratory thoracotomy, mediastinoscopy, excisional biopsy, or similar surgery allowed for diagnosing, staging, or determining potential resectability of lung tumor
• No prior chemotherapy or radiotherapy for lung cancer
• No prior radiotherapy to the neck or thorax
• At least 4 weeks since prior thoracic or other major surgery (excluding mediastinoscopy) and recovered
• More than 7 days since prior FNA, CNB, or mediastinoscopy
• No other concurrent anticancer therapy, including chemotherapy, radiotherapy, or biologic agents
• No other concurrent investigational drugs
• No concurrent major surgical procedures

• No concurrent full-dose anticoagulants (e.g., low-molecular weight and unfractionated heparin or warfarin)

  • Low-dose warfarin (i.e., 1 mg) is allowed to prevent clotting of an infusaport or central line
• No concurrent brachytherapy, radiopharmaceuticals, high linear energy transfer radiation (i.e., fast neutrons), particle therapy (i.e., protons, carbon, or helium), and/or altered fractionation schemes
• No concurrent intensity-modulated radiotherapy
• No concurrent prophylactic contralateral hilar or supraclavicular lymph node radiotherapy