PK Trial of Sorafenib & Erlotinib in Patients With Refractory Solid Tumors

You may be eligible if

• 1. Histologically confirmed incurable solid tumors refractory to standard treatment or for which there is no known standard treatment.
• 2. Two cohorts of patients will be enrolled: Cohort A will consist of patients who are current smokers, and Cohort B will consist of patients who are current nonsmokers. Nonsmokers are patients who have not consumed tobacco or nicotine-containing products for 1 year before the start of the study. Patients classified as current smokers must have smoked a minimum of 10 cigarettes per day for \<1 year.
• 3. Patients must have evaluable disease.
• 4. Recovery from any toxic effects of prior therapy to grade 1 per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
• 5. Completion of radiation therapy at least 21 days prior to the start of study treatment (not including palliative local radiation).
• 6. An Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• 7. Absolute neutrophil count (ANC) \>1,500/mL and platelets \>75,000/mL (within 7 days prior to study treatment).
• 8. Hemoglobin \>9 g/dL (within 7 days prior to treatment). Patients may be transfused or receive erythropoietin to maintain or exceed this level where otherwise indicated.
• 9. International normalized ratio (INR) \<1.5 or prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits (WNL) of the institution (if patient is not on anti-coagulation therapy; patients receiving anticoagulation treatment with an agent such as warfarin or heparin may be allowed to participate with the therapeutic range established prior to the initiation of study treatment).
• 10. Serum creatinine \<1.5 x the institutional upper limit of normal (ULN) within 7 days prior to study treatment. If the absolute value is greater than 2 mg/dL, the creatinine clearance (calculated according to the Cockcroft-Gault formula) must be \> 45 mL/min for the patient to be eligible for the study.
• 11. Transaminases \<3 x the institutional ULN (except if there is known hepatic metastasis, wherein transaminases may be \<5 x institutional ULN).
• 12. Total bilirubin \<1.5 times ULN.
• 13. Patients must be able to understand the nature of this study, give written informed consent, and comply with study requirements.
• 14. Agreement of female patients of childbearing potential and male patients who have partners of childbearing potential to use an effective form of contraception to prevent pregnancy during treatment, and for a minimum of 90 days thereafter. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
• Exclusion
• 1. Patients with untreated brain metastases. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis. Patients who have a history of brain metastases that has been treated by surgery or radiation therapy \> 4 weeks with no signs of Central Nervous System (CNS) progression are allowed.
• 2. Women who are pregnant or lactating.
• 3. Patients whose last dose of chemotherapy, immunotherapy, or investigational drug therapy was completed \< 21 days prior to receiving study drug
• 4. 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 (see Appendix B);
• * ventricular arrhythmia;
• * valvular heart disease.
• 5. Myocardial infarction (MI) within 6 months prior to initiation of study treatment.
• 6. Cardiomegaly on chest imaging or CHF \> Class 2 per NYHA classification (see Appendix B) unless the left ventricular ejection fraction (LVEF) is within normal range for the institution within 3 months of initiating therapy.
• 7. Poorly controlled hypertension (defined as systolic blood pressure \[BP\] \>150 mmHg and/or diastolic blood pressure \>90 mmHg on anti-hypertensive medications).
• 8. Unstable angina (anginal symptoms at rest).
• 9. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• 10. Presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
• 11. A serious active infection (\> grade 2) at the time of treatment
• 12. A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
• 13. A major surgical procedure within 28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study.
• 14. Any minor surgery must be completed within 7 days prior to beginning study treatment.
• 15. Use of rifampin, St. John's wort, or other potent inducers of CYP3A4 are not permitted from Day -14 through Day 15 of the study (see Appendix C).
• 16. Use of ketoconazole and other potent inhibitors of CYP3A4 are not permitted from Day -14 through Day 15 of the study (see Appendix C).
• 17. Stroke or transient ischemic attack (TIA) within the past 6 months.
• 18. Any prior history of hypertensive crisis or hypertensive encephalopathy.
• 19. Pulmonary hemorrhage/bleeding event \> grade 2 within 28 days of study treatment.
• 20. Any other non-pulmonary hemorrhage/bleeding event\> grade 3 within 28 days of study treatment.
• 21. Evidence or history of bleeding diathesis or coagulopathy.
• 22. Serious non-healing wound, ulcer, or bone fracture.
• 23. Known or suspected allergy/hypersensitivity to any agent given in the course of this trial.
• 24. Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease.
• 25. Patients who smoke 1-9 cigarettes per day during the year before study entry or patients who have smoked for \<1 year will not be eligible for this study.
• 26. Any condition that impairs the patient's ability to swallow whole pills.
• 27. Known human immunodeficiency virus (HIV) infection or chronic active Hepatitis B or C.