Sorafenib and Erlotinib or Sorafenib Alone in Advanced Non-Small Cell Lung Cancer Progressing on Erlotinib

Inclusion Criteria

• Histologically confirmed stage IIIB/IV or relapsed non-small cell lung carcinoma (squamous carcinoma, adenocarcinoma, or large cell carcinoma). Patients with mixed tumors with small-cell elements are ineligible.
• Patients with no more than 2 prior lines of therapy, with the latest of those therapies being single-agent erlotinib.
• Evidence of progressive disease on erlotinib as assessed by the treating physician. Erlotinib must be the last treatment for NSCLC prior to enrollment into this study. Patients may be on erlotinib until enrollment. If erlotinib has already been stopped, the period of time off Erlotinib cannot exceed 14 days prior to study enrollment.
• Patients must have experienced a clinical benefit (complete response [CR], partial response [PR], or stable disease [SD]) from prior therapy with erlotinib for a period of 8 weeks.
• Patient must have one measurable lesion measuring at least 10 mm in the longest diameter (LD) by spiral computed tomography (CT), or 20 mm with conventional techniques according to the Response Evaluation Criteria in Solid Tumors (RECIST).
• Recovery from any toxic effects of erlotinib to ≤ grade 1 per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
• Completion of palliative radiation therapy prior to the start of study treatment. Previously irradiated lesions in the advanced setting cannot be included as target lesions unless clear tumor progression has been observed following the completion of radiation therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Absolute neutrophil count (ANC) >=1, 500 and platelets >=75,000 (within 7 days prior to initial study treatment).
• Hemoglobin >=9 g/dL (within 7 days prior to initial treatment).
• International normalized ratio (INR) =45 mL/min to be eligible.
• Bilirubin =5 x institutional ULN.
• Patients must be able to understand the nature of this study, give written informed consent, and comply with study requirements.
• Agreement of male patients (with partners of childbearing potential) and female patients of childbearing potential to use effective contraception to prevent pregnancy during treatment and for a minimum of 90 days thereafter. Additionally, women should not breastfeed during this time.

Exclusion Criteria

• Past or current history of neoplasm other than the entry diagnosis, with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone, and a disease-free survival (DFS) >=3 years.
• Pregnancy or lactation. All females of child-bearing potential must have negative serum or urine pregnancy tests within 7 days prior to study treatment.
• Prior epithelial growth factor receptor (EGFR) inhibitors, with the exception of erlotinib, are not allowed. This includes both tyrosine kinase inhibitors (TKIs) and monoclonal antibodies. Prior vascular endothelial growth factor (VEGF) inhibitors, with the exception of bevacizumab, are not allowed.
• Significant cardiac disease within 90 days of starting study treatment including:
• superior vena cava syndrome
• new onset angina
• congestive heart failure (CHF) > Class 2 per New York Heart Association (NYHA) classification
• arrhythmia
• valvular heart disease.
• Myocardial infarction within 6 months prior to initiation of study treatment
• Cardiomegaly on chest imaging or ventricular hypertrophy on electrocardiogram (ECG) unless the left ventricular ejection fraction (LVEF) is within normal range for the institution.
• Poorly controlled hypertension (defined as systolic blood pressure [BP] >150 mm Hg and/or diastolic BP >100 mm Hg on antihypertensive medications).
• Unstable angina (anginal symptoms at rest).
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.