Trial of Carboplatin/Paclitaxel/Cetuximab in Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria:

To be eligible for the study, subjects must fulfill all of the following criteria and have a complete signed informed consent form.

• Subjects must have signed an approved informed consent.
• Subjects with histologically or cytologically documented stage IIIB (supraclavicular lymph node, high neck node, or pleural effusion involvement) or IV NSCLC. Disease must be newly diagnosed or recurrent at least 1 year post adjuvant therapy.
• Subjects with measurable disease.
• Subjects with ECOG performance status 0-1.
• Subjects with asymptomatic brain metastasis are eligible; however, they must have completed radiotherapy/radiosurgery at least 2 weeks prior to enrollment and be off steroids.
• Radiotherapy must have been completed > 2 weeks prior to enrollment and the subject must have recovered from all adverse effects of prior radiotherapy. No previous irradiation to the only area of measurable disease. New lesions that developed in a previously irradiated area will be allowed.
• If diagnostic tissue or slides are available for a subject, these must be submitted for testing of EGFR status.
• Subjects ≥18 years of age.
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea ≥12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level >35mIU/mL]. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.

• Subjects with adequate hematologic function defined as: ANC ≥1,500/mm 3 ; WBC

  ≥3,000/mm 3 ; platelets ≥100,000/mm 3 ; and hemoglobin ≥9 g/dL.

• Subjects with adequate hepatic function defined as: total bilirubin ≤1.5 x upper limit of normal (ULN) or AST ≤2.5 x ULN.
• Subjects with adequate renal function defined as a serum creatinine level ≤1.5 mg/dL or a creatinine clearance ≥60 cc/minute.

Exclusion Criteria:

Any of the following criteria will make the subject ineligible to participate in this study.

• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study. Subjects who are men must also agree to use effective contraception.
• WOCBP using a prohibited contraceptive method.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or prior to study drug administration.
• Subjects who have had prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for 5 years.
• Subjects with significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure, cardiomyopathy with decreased ejection fraction, myocardial infarction within the past year, or cardiac ventricular arrythmias requiring medication.
• Subjects with an uncontrolled seizure disorder, or active neurological disease.
• Subjects with symptomatic brain metastasis. Prohibited Therapies and/or Medications
• Subjects who have received prior systemic chemotherapy. Subjects with no more than one prior adjuvant regimen for initially diagnosed disease are eligible for the study.
• Subjects with a history of prior cetuximab or other therapy that specifically and directly targets the EGFR pathway.
• Subject with prior severe infusion reaction to a monoclonal antibody.
• Subjects with know allergy to Cremophor EL.
• Subjects with known peripheral neuropathy (> grade 1).
• Subjects with prior erythropoietin (i.e., Epogen, Procrit) treatment.
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness.