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