BATTLE Program: Sorafenib in Patients With NSCLC

Primary Objective:

* To determine the 8 week progression-free survival rate (i.e. disease control rate) in patients with advanced non-small cell lung cancer (NSCLC) who have failed at least one prior chemotherapy regimen.

Secondary Objective:

The secondary objectives of this study will be to:

* Determine the overall response rate
* Determine the overall survival
* Determine the time to disease progression
* Assess the safety/toxicity of the study treatment
* Assess biomarker modulation in the tumor tissue and serum samples from the treatment.
* Assess plasma and intra-tumor concentrations of study treatment

BAY 43-9006® (Sorafenib) is an experimental agent designed to stop the growth of cancer cells.

In order to enroll in this study, you must also be enrolled in Protocol 2005-0823: A Biomarker-integrated study in Chemorefractory patients with advanced Non-Small Cell Lung Cancer. Protocol 2005-0823 is the screening study in a group of studies called the BATTLE program. Participants in Protocol 2005-0823 are assigned to one of the treatment studies. The results of your tumor analysis helped the study doctor determine to assign you to this particular treatment study.

While on study, you will take 2 tablets of sorafenib each morning, and again each evening. Sorafenib should be taken with about 1 cup of water on an empty stomach (either 1 hour before a meal or 2 hours after a meal). Sorafenib must be swallowed whole without chewing. If you feel nauseated before or after taking the medication, anti-nausea medications should be used. If you miss a dose, you should skip it and take the next scheduled dose at the right time. Your medication should be stored at room temperature.

Every 4 weeks (1 cycle) your complete medical history will be recorded and you will have a physical exam, including measurement of vital signs (blood pressure, pulse, temperature, and breathing rate) and weight. Blood (about 2 teaspoons) and urine will be drawn for routine tests. You will have a performance status evaluation (questions about your ability to perform everyday activities) and blood drawn (about 1-2 teaspoons) to check your blood clotting function. Your study doctor will also ask you about any medications you are taking and your smoking history. You will be asked to record your weekly blood pressure for the first 6 weeks of study treatment. The study doctor or research nurse will review the log at each clinic visit.

Every 2 cycles, your tumor will be evaluated by chest x-ray and computed tomography (CT) or magnetic resonance imaging (MRI) scans to evaluate the status of the disease. If you are taking Coumadin® (warfarin), you will have blood drawn (about 1-2 teaspoons) to check your blood clotting function weekly for the first 6 weeks of treatment and then every cycle after that.

You may continue receiving sorafenib for as long as the cancer responds to study treatment. Your doctor may decide to take you off this study if you experience intolerable side effects or your medical condition gets worse. If you stop study treatment, you will be allowed to enroll in one of the remaining 3 protocols of the BATTLE program.

After you have stopped taking the study treatment, you will have a physical exam, including measurement of vital signs. Blood (about 2 teaspoons) and urine will be collected for routine tests. You will also have blood drawn (about 1-2 teaspoons) to check your blood clotting function. You will have a performance status evaluation, a chest x-ray, and a CT or MRI scan. Following this evaluation, you will be contacted by telephone every 3 months for up to 3 years, to see how you are doing.

You have the right to leave the study at any time. If you choose to stop participating in this study, you should contact the study chair and/or research nurse. Your doctor may decide to take you off this study if your medical condition gets worse and/or you are unable to comply with study requirements.

This is an investigational study. Sorafenib (BAY 43-9006) has been approved by the FDA for treatment of advanced renal cell cancer; however, it's use in this research study is investigational. Up to 62 patients will take part in this multicenter study. Up to 50 will be enrolled at M. D. Anderson.

Eligibility Criteria:
Inclusion Criteria:

1. The patient has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or fine-needle aspiration.
2. The patient has a diagnosis of either stage IIIB, stage IV, or advanced, incurable NSCLC, and failed at least one front-line metastatic NSCLC chemotherapy regimen. (Patients who have failed adjuvant or locally advanced therapy within 6 months are also eligible to participate in study).
3. The patient has uni-dimensionally measurable NSCLC.
4. Karnofsky performance status \>/= 60 or ECOG performance status 0-2
5. The patient has biopsy accessible tumor.
6. The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) \>/= 1,500/mm\^3, platelet count \>/= 100,000/mm\^3, white blood count (WBC) \>/= 3,000/ mm\^3, and hemoglobin \>/= 9 g/dL.
7. The patient has adequate hepatic function as defined by a total bilirubin level \</= 1.5 \* the upper limit of normal, and alkaline phosphatase, AST or ALT \</= 2.5 \* the upper limit of normal.
8. The patient has adequate renal function as defined by a serum creatinine level \</= 1.5 mg/dL or a calculated creatinine clearance of \>/= 60cc/minute.
9. The patient has Prothrombin time (PT) \< 1.5 \* upper limit of normal
10. If patient has brain metastasis, they must have been stable (treated or asymptomatic) for at least 4 weeks after radiation if treated with radiation and not have used steroids for at least 1 week. Re-imaging performed after 2 weeks, upon completion of radiation therapy.
11. The patient is \>/= 18 years of age.
12. The patient has signed informed consent.
13. The patient is eligible if disease free from a previously treated malignancy, other than a previous NSCLC, for greater than two years. Patients with a history of prior basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix are exempt from exclusion.
14. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.Childbearing potential will be defined as women who have had menses within the past 12 months,who have not had tubal ligation or bilateral oophorectomy.Should a woman become pregnant or suspect that she is pregnant while participating in this study,she should inform her treating physician immediately.The patient,if a man,agrees to use effective contraception or abstinence.
15. Subject must be considered legally capable of providing his or her own consent for participation in this study.

Exclusion Criteria:

1. The patient has received prior investigational therapy, chemotherapy, surgery, or radiotherapy within 4 weeks of initiating study drug
2. The patient has undergone prior thoracic or abdominal surgery within 28 days of study entry, excluding prior diagnostic biopsy.
3. The patient has received radiation therapy to the measurable tumor within 6 months. Patients are allowed to have local irradiation for the management of tumor-related symptoms (bones, brain). However, if a patient has active new disease growing in the previously irradiated site, the patient will be eligible to participate in the study.
4. The patient has a significant medical history or unstable medical condition (unstable systemic disease: congestive heart failure (New York Heart Association Functional Classification class II or worse), recent myocardial infarction within 3 months, unstable angina, active infection (i.e. currently treated with antibiotics), uncontrolled hypertension). Patients with controlled diabetes will be allowed. Patient must be able to undergo procedure for tissue acquisition.
5. The patient has uncontrolled seizure disorder, active neurologic disease, or neuropathy \>/= grade 2. Patients with meningeal or central nervous System (CNS) involvement by tumor are eligible for the study if the above exclusion criteria are not met.
6. The patient is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding.
7. Any condition that is unstable or could jeopardize the safety of the patient and its compliance in the study, in the investigator's judgment.
8. The patient is actively taking herbal remedies or over-the-counter biologics (e.g., shark cartilage, high dose antioxidants).
9. Patients will be allowed to have prior biologic (i.e. Vascular endothelial growth factor (VEGF), epidermal growth factor family (EGFR), etc.) therapy. However, the patient will be excluded from a given study if he/she has received the same therapy as the clinical trial (i.e. If a patient has been previously treated with bevacizumab, they are allowed to enroll in any of the 4 studies. If a patient has been previously treated with erlotinib, they are excluded from the clinical trials with erlotinib). In addition, if a patient has been previously treated with gefitinib (Iressa), they are excluded from the clinical trials with erlotinib.
10. Prior hemoptysis or bleeding diathesis.
11. Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
12. Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
13. History of seizure disorder requiring medication (such as steroids or anti-epileptics).
14. History of organ allograft and bone marrow transplant
15. Previous malignancy (except for cervical carcinoma in situ, adequately treated basal cell carcinoma, or superficial bladder tumors \[Ta, Tis \& T1\] or other malignancies curatively treated \> 3 years prior to entry).
16. Patients with clinically significant bleeding (e.g., gastrointestinal bleeding) within the past month prior to study entry are ineligible.
17. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 48 hours of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures (e.g., cervical cap, condom, and diaphragm) during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between BAY 43-9006 and oral contraceptives.
18. Substance abuse, medical, psychological or social conditions that, in the judgment of the investigator, is likely to interfere with the patient's participation in the study or evaluation of the study results.
19. Known allergy to the investigational agent or any agent given in association with this trial.
20. Concurrent use of St. John's Wort, Rifampicin, and/or ritonavir.