Sorafenib and Thoracic Radiation for Patients With Non-Small Cell Lung Cancer

The Study Drug:

Sorafenib is designed to block the function of important proteins in cancer cells. These
proteins, when active, are in part responsible for the growth and behavior of cancer cells.

Study Drug Dose Escalation:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you joined this study. Up to 4 groups of 3-6 participants will be
enrolled in the Phase I portion of the study.

Enrolled in the Phase I portion, the dose of sorafenib you receive will depend on when you
joined this study. The first group of participants will receive the lowest dose level of
sorafenib. Each new group will receive a higher dose of sorafenib than the group before it,
if no intolerable side effects were seen. This will continue until the highest tolerable dose
of sorafenib is found.

All participants will receive the same type and amount of radiation.

Study Drug Administration:

You will take sorafenib capsules 1-2 times every day beginning on Day 1 of radiation therapy.
If you are in the first group on study, you will take the study drug 1 time. If you are in
any other groups, you will take the study drug 2 times a day. You will take the study drug
without food (1 hour before or 2 hours after eating).

Radiation Therapy:

Before receiving radiation therapy, you will have a "marking session". At this visit, you
will have a computed tomography (CT) scan that will be used to help to plan out the radiation
therapy. This will take about 45 minutes.

Before receiving radiation, you will also have a single photon computed tomography (SPECT)
scan of your lungs.

You will be given 15 radiation treatments, once a day, 5 days a week, Monday-Friday. Each
treatment will take about 30 minutes. You will sign a separate consent form for radiation
therapy and the procedure will be described to you in more detail.

Clinical Visits:

You will have routine clinical visits every week while receiving radiation therapy. The
information collected during these clinical visit will be used for the study. At these
visits, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your blood pressure and weight.

- You will be asked about any side effects you may be experiencing and any new drugs you
may be taking.

- You will be asked how well you are able to perform the normal activities of daily living
(performance status evaluation)

- Blood (about 3-4 teaspoons) will be drawn for routine tests.

- You will have any tests that doctor feels medically necessary

Urine will be collected every week while you are taking sorafenib and receiving radiation
therapy for routine tests.

Length of Study:

You will remain on study for 6 weeks after you complete radiation therapy. You will be taken
off the study early if the disease gets worse or intolerable side effects occur.

End-of-Study Visit:

You will have an end-of-study visit 4-6 weeks after you stop receiving radiation. At this
visit, you will have a CT scan to check the status of the disease.

Follow-Up Visits:

Your first follow-up visit will be at 6 weeks (+/- 7 days) after radiation therapy and the
second follow-up appointment will be at 10 weeks (+/- 7 days) after radiation therapy. You
will then have follow up visits every 3 months. At these visits, you will go though the
following:

- Your complete medical history will be recorded.

- You will have a physical exam, including measurement of your weight and blood pressure.

- You will be asked how well you are able to perform the normal activities of daily living
(performance status evaluation).

- You will be asked about any drugs you may be taking.

- Blood (about 3-4 teaspoons) and urine will be collected for routine tests.

- You will also have chest x-ray.

- You will have a computed tomography (CT) scan of your chest area.

- The location, type, and size of all measurable lesions will be recorded.

- If your doctor thinks it is necessary, you will have a positron emission
tomography(PET)/CT scan.

- If your doctor thinks it is necessary, you will have an electrocardiogram (ECG -- a test
that measures the electrical activity of the heart).

- You may have a lung perfusion scan to see if all regions of your lung are equally
functional or not. This is called lung SPECT scan.

- You will have a lung functional test (PFT) if your doctor thinks it is necessary.

All these tests are routine examinations as you would have without participating in this
study in order to know the status of the disease.

This is an investigational study. Sorafenib is FDA approved and commercially available for
renal cell carcinoma. The radiation therapy schedule used for this study is standard
treatment for lung cancer patients. The use of sorafenib with radiation therapy is
investigational.

Up to 64 patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Pathologically proven previously untreated or systemically treated poor prognosis
NSCLC patients for whom palliative thoracic irradiation is the treatment of choice per
standard of care.

2. Patients for whom palliative thoracic irradiation therapy to 45 Gy/15 FX is the
recommended treatment by their treating radiation oncologist.

3. The primary tumor and/or regional lymphatic metastases must be evaluable
radiographically.

4. Age >/= 18 years or older.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 or greater, weight
loss
6. No prior radiation to the thorax.

7. Adequate bone marrow, liver and renal function as assessed by the following: *
Hemoglobin >/= 9.0 g/dl * Absolute neutrophil count (ANC) >/=1,000/mm^3 *Platelet
count >/ =100,000/mm^3 * Total bilirubin
8. Patients with distant metastasis are eligible.

9. Women of childbearing potential must have a negative serum pregnancy test performed
within 7 days prior to the start of treatment

10. Women of childbearing potential and men must agree to use adequate contraception
(barrier method of birth control) prior to study entry and for the duration of study
participation. Men should use adequate birth control for at least three months after
the last administration of sorafenib.

11. Ability to understand and the willingness to sign a written informed consent. A signed
informed consent must be obtained prior to any study specific procedures.

12. INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation
treatment with an agent such as warfarin or heparin may be allowed to participate. For
patients on warfarin, the INR should be measured prior to initiation of sorafenib and
monitored at least weekly, or as defined by the local standard of care, until INR is
stable.

13. Patients must sign an informed consent indicating that they are aware of the
investigational nature of the study in keeping with the policy of M.D. Anderson Cancer
Center. The only approved consent form is attached to this protocol.

Exclusion Criteria:

1. Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have
unstable angina (anginal symptoms at rest) or new onset angina (began within the last
3 months) or myocardial infarction within the past 6 months.

2. Known hemorrhagic brain metastasis. Patients with neurological symptoms must undergo a
CT scan/MRI of the brain to exclude hemorrhagic brain metastasis.

3. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

4. Uncontrolled hypertension defined as systolic blood pressure > 140 mmHg or diastolic
pressure > 90 mmHg, despite optimal medical management.

5. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.

6. Active clinically serious infection > CTCAE Grade 3.

7. Thrombolic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months.

8. Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of
study drug.

9. Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of
study drug.

10. Serious non-healing wound, ulcer, or bone fracture.

11. Evidence or history of bleeding diathesis or coagulopathy

12. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
study drug.

13. Current use of St. John's Wort or rifampin (rifampicin).

14. Known or suspected allergy to sorafenib.

15. Any malabsorption problem.

16. Patients with squamous cell carcinoma.