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