IRB Number:

05-004303

Trial Status:

Open for Enrollment

Phase: I

Why is this study being done?

This study is being done to learn:
-About the side effects (good or bad) of BAY 43-9006 (Sorafenib), carboplatin, paclitaxel and bevacizumab when given together;
-The highest safe dose of the cancer drug called BAY 43-9006 that can be given with carboplatin, paclitaxel and bevacizumab to patients with advanced nonsmall cell lung cancer;
-If BAY 43-9006, carboplatin, paclitaxel and bevacizumab fight the patient's cancer when given together;
-How much BAY 43-9006, carboplatin, paclitaxel and bevacizumab are in the patient's blood at specific times after they take the drugs.
Sorafenib, paclitaxel, carboplatin and bevacizumab have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of cancer, but have not been approved in the combination used in this study. Therefore, the use of this combination is investigational.

Who is Eligible to Participate in the Study?

- Age 18 or older
-Diagnosed with Stage IIIB (with malignant pleural effusions) or Stage IV Non-Small Cell Lung Cancer (NSCLC)
- Previously Untreated

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

Before starting any study treatment, patients will have certain tests and procedures to determine whether they can take part in this study. The study doctor will look at the patient's medical history, patients will have a physical exam, their lung cancer will be evaluated by CT scan or MRI, patients will have an electrocardiogram (a test which measures the electrical activity of the heart), urine tests, and patients will also have standard and research blood tests. If patient is a woman who can become pregnant, they will also have a blood pregnancy test.

Patients will receive four different drugs during their treatment. Treatment on this two-part study will follow a three-week schedule, and each three-week period is known as a cycle. In the first part of the study, the researchers are trying to find out the highest dose of the study drugs that can be safely given together. In the second part of the study, the researchers are trying to find out more about the highest dose of the study drugs that were safely given together in the first part of the study.

To find the highest dose of sorafenib, paclitaxel, carboplatin and bevacizumab that can be given together, the first group of six patients will receive lower doses of sorafenib and bevacizumab. The doses of paclitaxel and carboplatin are the standard doses and will stay the same for up to six cycles of the study for all patients who complete six cycles. If the first 5 or 6 patients do not have severe side effects, the doses of sorafenib and bevacizumab will then be increased until at least some patients have severe side effects. The dose that the patient gets will not increase during the study, but if they have bad side effects, their dose of sorafenib, bevacizumab, paclitaxel or carboplatin may be lowered at future visits. All patients will be watched carefully for any serious side effects. These side effects cannot be completely known ahead of time. This study may involve significant risks for this reason.

Patients in Part 1 and Part 2 will be given bevacizumab, paclitaxel and carboplatin in their vein on the first day of every three week cycle. They will take sorafenib by mouth twice a day on days 3-19 during Cycle 1 and days 2-19 of every three week cycle thereafter. The three-week cycle of treatment with bevacizumab, paclitaxel, carboplatin and sorafenib will be repeated up to six times as long as the patient does not have serious side effects and their cancer does not get worse. After that the patient may receive additional three-week cycles of sorafenib and bevacizumab as long as they do not have serious side effects and their cancer does not get worse.

Patients in Part 1 will have their treatment during cycles 1 and 2 in the Clinical Research Unit (CRU) at St. Marys Hospital. Beginning at cycle 3, patients will have their treatment as an outpatient on Gonda 10. During the treatment, patients will have their blood pressure (checked twice at each visit), temperature and pulse checked during the drug infusions. Patients will need to remain in the treatment room for one to two hours after the infusions are completed.

Patients in both Parts 1 and 2 will have blood tests and a urinalysis every week. These tests are needed to measure their blood cell counts and to check their urine for protein. CT scans, bone scans, and magnetic resonance imaging (MRI) tests may also be done to measure the cancer after every other cycle or sooner if the doctor considers that this is necessary. Some of the blood tests and the CT scans, bone scans, and MRI tests are part of the routine care given to cancer patients.

In addition to the regular blood tests, patients will also have other blood and urine samples collected for research purposes. Some of the research blood tests will look at the study drug levels in the patient's body. To measure the study drug levels in the patient's blood, some of the patient's blood samples will be sent to a laboratory outside Mayo. All of these tests will be done during Cycle 1 and Cycle 2 on days 1, 2, 3, and 15. Patients will have a catheter (thin, flexible tube) placed in a vein in their arm to allow these blood samples to be collected without the discomfort of many needle punctures.

If the patient and their research doctor decide that the patient will have more than one cycle of this treatment, patients will have their intravenous study drug treatments for cycle 2 in the CRU as an inpatient. Patients will have an electrocardiogram, which is not routine care and is paid for by the study, at the beginning of the study and at the end of the study. Patients will also have some blood tests to measure blood chemistries and blood clotting more frequently than is standard of care and these extra blood tests will be paid for by the study.

If the patient and their research doctor decide that the patient will have more than two cycles of this treatment, patients will have their intravenous study drug treatments on Gonda 10 in the Research Treatment Unit as an outpatient. A research blood sample of about 10 ml (2 teaspoons) will be drawn on Day 1 of Cycles 3 and 4.

Should the patient stay on the study for longer than cycle 6, they will not receive further treatment with paclitaxel and carboplatin, as standard of care is up to six cycles of
treatment with these two drugs. However, patients will receive sorafenib and bevacizumab, at no cost to the patient for the drugs, until the patient has bad side effects, the patient decides to stop, or if the patient's cancer gets worse.

How long will the Study run?

Patients will be in the study until the side effects are too bad, or they decide to stop, or if their cancer gets worse.

Sponsor(s): Bayer

Study Activation/Registration Date: 06/23/2006

IRB Review and Approval Date: 12/23/2005

Study Type: Dosing/Treatment

Projected Accrual: The plan is to have up to 60 patients participate from multiple medical centers.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Julian R. Molina, PhD, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 05/23/2008