Bevacizumab, Paclitaxel, Carboplatin, and Radiation Therapy to the Chest in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed non-small cell lung carcinoma (NSCLC) meeting the following criteria:

  • The following subtypes are eligible:

    • Adenocarcinoma (including bronchoalveolar)
    • Large cell carcinoma (including giant and clear cell carcinomas)
    • Poorly differentiated carcinoma
  • No squamous cell histology
  • Unresectable stage II-III disease
  • Tumor must not invade the trachea or major arterial or venous structures

• Measurable or evaluable disease

  • Measurable disease defined as ? 1 lesion that can be accurately measured in ? 1 dimension as ? 20 mm with conventional techniques or as ? 10 mm with spiral CT scan
• No evidence of CNS disease, including primary brain tumor or brain metastases
• ECOG performance status (PS) 0-1 or Karnofsky PS 60-100%
• Life expectancy > 6 months
• Granulocyte count ? 1,500/mm³
• Platelet count ? 100,000/mm³
• Bilirubin < 1.25 times upper limit of normal (ULN)
• AST < 2.5 times ULN
• Creatinine normalOR creatinine clearance ? 60 mL/min
• FEV_1 ? 1.0 liters
• 24-hour urine protein < 1,000 mg (for patients with urine protein:creatinine ratio [by urine analysis] > 1.0)
• No hemoptysis within the past 12 months (defined as bright red blood in sputum of > 1 teaspoon)
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No history of allergic reactions attributed to carboplatin or taxane
• No serious or nonhealing wound, ulcer, or bone fracture
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• No significant traumatic injury within the past 14 days

• No clinically significant cardiovascular disease, including any of the following:

  • Cerebrovascular accident within the past 6 months
  • Uncontrolled hypertension
  • Myocardial infarction or unstable angina within the past 6 months
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Unstable angina pectoris
  • Clinically significant peripheral vascular disease
• No known bleeding diathesis or coagulopathy
• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)

• No uncontrolled intercurrent illness including, but not limited to, the following:

  • Ongoing or active infection
  • Psychiatric illness or social situations that would limit study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ? 6 months after completion of study treatment
• No HIV positivity
• No prior chemotherapy
• No prior epidermal growth factor receptor-targeted therapy
• No prior vascular endothelial growth factor-targeted therapy
• No prior chest radiotherapy
• No major surgery or open biopsy within the past 14 days

• No concurrent treatment with full-dose anticoagulation

  • Low-dose anticoagulants (e.g., warfarin) to maintain patency of central venous catheter allowed provided all of the following criteria are met:

    • Daily dose of warfarin < 1 mg
    • INR < 1.5
• No other concurrent investigational agents
• No concurrent major surgical procedures
• No other concurrent anticancer agents or therapies
• No concurrent chronic treatment with aspirin (> 325 mg daily) or nonsteroidal anti-inflammatory agents
• No dexamethasone as an antiemetic during chemoradiotherapy
• No colony-stimulating factors during chemoradiotherapy