A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab With or Without Concurrent Cetuximab in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC),
including any of the following subtypes:

- Adenocarcinoma

- Large cell carcinoma

- Squamous cell carcinoma

- Unspecified

- Newly diagnosed stage IV disease OR recurrent disease after prior surgery and/or
irradiation

- Patients with additional lesions in an ipsilateral non-primary lobe without M1a
or M1b disease are not considered to have stage IV disease and are not eligible

- Measurable or non-measurable disease documented by CT scan or MRI

- Pleural effusions, ascites, and laboratory parameters are not acceptable as the
only evidence of disease

- Measurable disease must be outside a previously irradiated field or must have
progressed

- Patients must not have received prior chemotherapy for any stage NSCLC

- Brain metastases allowed provided they have been controlled for ≥ 2 weeks after
completion of treatment and there is no residual neurological dysfunction while off
corticosteroids for at least 1 day

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-1

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL

- Serum creatinine normal

- Creatinine clearance ≥ 50 mL/min

- Urine protein:creatinine ratio ≤ 0.5 OR 24-hour urine protein < 1,000 mg (for
patients who will be receiving bevacizumab)

- Serum bilirubin ≤ 2 times upper limit of normal (ULN) (≤ 5 times ULN for patients
with liver metastases)

- SGOT OR SGPT ≤ 2 times ULN (≤ 5 times ULN for patients with liver metastases)

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for 3-6 months after
completion of study treatment

- Agrees to submission of specimens that is sufficient for EGFR FISH testing and other
translational medicine studies

- Willing to provide prior smoking history

- No significant traumatic injury within the past 28 days

- No symptomatic sensory neuropathy ≥ grade 2 as assessed by NCI CTCAE v3.0

- No documented presence of human anti-mouse antibodies

- No documented evidence of acute hepatitis

- No active or uncontrolled infection

- None of the following within the past 6 months:

- Cerebrovascular accident, myocardial infarction, or unstable angina

- Uncontrolled hypertension

- NYHA class II-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Clinically significant peripheral vascular disease

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies (e.g., trastuzumab [Herceptin®] or epoetin alpha)

- No other prior malignancy except for any of the following:

- Adequately treated basal cell or squamous cell skin cancer

- In situ cervical cancer

- Adequately treated stage I or II cancer from which the patient is currently in
complete remission

- Any other cancer from which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Prior radiotherapy allowed provided patients have recovered from all associated
toxicities at the time of study registration

- No prior cetuximab, gefitinib, erlotinib, or other investigational agents that target
the EGFR pathway

- Patients must not have received prior platinum-based chemotherapy for any purpose

- No prior bevacizumab or VEGF-related agents

- No prior chimerized or murine monoclonal antibody therapy

- At least 28 days since prior surgery (thoracic or other major surgeries) or open
biopsy and recovered (for patients who are bevacizumab-appropriate AND bevacizumab is
planned)

- More than 7 days since prior core biopsy

- No concurrent major surgical procedures