Carboplatin and Paclitaxel Combined With Cetuximab and/or IMC-A12 in Patients With Advanced Non-Small Cell Lung Cancer

Inclusion Criteria:

* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

  * Stage IIIB disease

    * T4, NX with nodule in ipsilateral lung lobe allowed provided patient is not a candidate for combined chemotherapy and radiotherapy
  * Stage IV disease (includes M1a and M1b)
* Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
* Ineligible for or refused treatment with bevacizumab
* No untreated or symptomatic central nervous system (CNS) metastases

  * Patients with a history of CNS metastases that are definitively treated, stable, and controlled are eligible provided the following criteria are met:

    * Definitive therapy (surgery and/or radiotherapy) has been administered
    * Not planning to undergo additional treatment for brain metastases
    * Clinically stable
    * Off corticosteroids or on a stable dose of corticosteroids for ≥ 14 days before study entry
* ECOG performance status 0-1
* Leukocytes \> 3,000/mm\^3
* Absolute neutrophil count (ANC) \> 1,500/mm\^3
* Hemoglobin \> 9 g/dL
* Platelet count \> 100,000/mm\^3
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
* Aspartate Aminotransferase (AST) \< 3 times ULN (\< 5 times ULN if elevations due to liver metastases)
* Creatinine \< 1.5 times ULN OR creatinine clearance \> 60 mL/min
* Fasting serum glucose \< 120 mg/dL
* Partial thromboplastin time (PTT) ≤ 1.2 times ULN and international normalized ratio (INR) ≤ 1.5 (unless patient is on anticoagulation therapy)
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 3 months after the last dose of cixutumumab
* No poorly controlled diabetes mellitus

  * Patients with a history of diabetes mellitus are eligible provided their blood glucose is within normal range and they are on a stable dietary or therapeutic regimen for this condition
* No other prior or concurrent malignancy, except for the following:

  * Curatively treated malignancy with no known active disease for ≥ 3 years AND is considered to be at low risk for recurrence by the treating physician
  * Adequately treated nonmelanoma skin cancer or lentigo maligna with no evidence of disease
  * Adequately treated cervical carcinoma in situ with no evidence of disease
  * Prostatic intraepithelial neoplasia with no evidence of prostate cancer
* Concurrent therapeutic anticoagulation allowed provided there is no bleeding and patient is on a stable dose of anticoagulation therapy (e.g., Warfarin with an INR of 2-3) for \> 2 weeks prior to study entry
* At least 21 days since prior radiotherapy
* More than 4 weeks since prior major surgery or hormonal therapy (other than hormone replacement therapy) and recovered
* More than 1 year since prior neoadjuvant or adjuvant chemotherapy

Exclusion criteria:

* Small cell lung cancer or mixed small cell and NSCLC
* History of allergic reactions attributed to compounds of similar chemical or biological composition to cixutumumab
* History of any medical or psychiatric condition, addictive disorder, or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study treatments or may interfere with the conduct of the study or interpretation of study results
* Prior agents targeting the EGFR or Insulin-like growth factor (IGFR) pathways
* Prior therapy for advanced NSCLC, except for surgery and/or radiotherapy
* Prior systemic therapy, including bevacizumab for advanced stage NSCLC
* Pregnant or nursing
* Peripheral neuropathy \> grade 1 as per Common Terminology Criteria for Adverse Event (CTCAE) v 4.0
* History of or suspected interstitial pneumonitis or pulmonary fibrosis on imaging
* Significant uncontrolled cardiac disease within the past 6 months, including any of the following:

  * Uncontrolled hypertension (BP \> 150/100 mm Hg)
  * Unstable angina
  * Recent myocardial infarction
  * Uncontrolled congestive heart failure
  * Cardiomyopathy with decreased ejection fraction
* Arterial thrombosis, pulmonary embolus, deep vein thrombosis, or hemorrhagic disorders within the past 28 days