IRB Number:

07-005703

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

Patients are being asked to take part in this research study because they have non-small cell lung cancer, which has been removed by a surgeon. This research is being done because even with the most aggressive after-surgery treatment with chemotherapy, many people still have the lung cancer recur (come back).
The purpose of this study is to determine if adding the new drug bevacizumab to chemotherapy improves the chance for cure for patients who have had surgery for the removal of the lung cancer. The research staff will compare the effects (good and bad) of adding bevacizumab to chemotherapy with standard chemotherapy alone on the patient and their lung cancer to see which is better at preventing the cancer from coming back.

Who is Eligible to Participate in the Study?

-Age 18 or older
-Diagnosed with non-small cell lung cancer, which has been removed by a surgeon
-Patient is no less than six weeks and no more than 12 weeks post-surgery at time of randomization

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

What is Involved With this Study?

If agreeing to be in the study, patients will be asked to participate in the following:
Patients will be "randomized" into one of the study arms described below in the section called "Procedures". Randomization means that the patient is put into a treatment arm by chance (as in the flip of a coin). The patient will have an equal chance of being placed in either arm. The patient and their study doctor will NOT be able to choose which arm the patient will be in. The study doctor will, however, choose which particular chemotherapy regimen within either study arm the patient will receive.

If taking part in this study, the patient will have the following tests and procedures:

Tests
- History and Physical exam every three weeks initially, then every six weeks for up to one year.
NOTE: If the patient is on Arm B, they will have their weight and blood pressure checked every three weeks for the first year.
- Blood work (CBC, chemistries, coagulation tests):
o If the patient is on Arm A:
-chemotherapy regimen 1 or regimen 3 twice every three weeks for the first 12 weeks, then every six weeks for up to one year
-chemotherapy regimen 2 every three weeks for the first 12 weeks, then every six weeks for up to one year;
o If you are on Arm B:
- chemotherapy regimen 1 or regimen 3 twice every three weeks for the first 12 weeks, then every three months for up to one year.
-chemotherapy regimen 2 every three weeks for the first 12 weeks, then every three months for up to one year.
- X-Rays including computed tomography (CT) scans every three months for up to one year.
- Urinalysis every 3-6 weeks for patients on arm B for up to one year.
- Pregnancy test (where appropriate) one time only.
- Electrocardiogram (ECG) one time only.

Some of these tests would be done even if the patient does not take part in the study.

Procedures
If the patient is on Arm A:
Treatment will be with one of three chemotherapy regimens, which will be chosen by the patient and their study doctor. All patients will receive what is felt to be a standard form of chemotherapy to be given as an outpatient. Only the combination of cisplatin and vinorelbine in patients with early stage lung cancer who have had the cancer removed (adjuvant chemotherapy) has been shown to improve survival. The other two chemotherapy regimens in this study, cisplatin and docetaxel or cisplatin and gemcitabine have not been tested as adjuvant chemotherapy. They have, however, been proven to been as active, or perhaps even more active, than the combination of cisplatin and vinorelbine for patients who have metastatic lung cancer (lung cancer that has spread to other parts of the body). It is therefore felt by most doctors that they will work just as well as cisplatin and vinorelbine as adjuvant chemotherapy and that is why they are options in this trial.

The three options are:

Regimen 1: Cisplatin and Vinorelbine will each be given on day one and repeated every three weeks for up to four treatment cycles. The vinorelbine only will be repeated on day 8 of the treatment cycle (i.e. one week after the
two chemotherapy drugs are given together, the vinorelbine alone will be given). The study drugs will be administered through a vein in the patient's arm.

The vinorelbine will be administered over about 5 to 10 minutes, the cisplatin over 60 minutes. On chemotherapy days that include cisplatin (day 1 of each cycle) the patient will also receive fluids by vein. The procedure will take up to eight hours. These fluids will be to keep the patient well hydrated and will consist of sterile salt water (saline solution) with extra minerals (potassium and magnesium) to help protect the patient's kidneys from the chemotherapy. The patient may also receive a diuretic, a medication to help the kidneys remove this fluid from their body and protect the kidneys from damage. The patient will not need these on day 8 (vinorelbine alone).

Regimen 2: Cisplatin and Docetaxel will each be given on day one and repeated every three weeks for up to four treatment cycles. The study drugs will be administered through a vein in the patient's arm. The docetaxel will be administered over 60 minutes, the cisplatin over 60 minutes. On chemotherapy days the patient will also receive fluids by vein. The procedure will take up to eight hours. These fluids will be to keep the patient well hydrated and will consist of sterile salt water (saline solution) with extra minerals (potassium and magnesium) to help protect their kidneys from the chemotherapy. The patient may also receive a diuretic, a medication to help the kidneys remove this fluid from their body and protect the kidneys from damage.

Regimen 3: Cisplatin and Gemcitabine will each be given on day one and repeated every three weeks for up to four treatment cycles. The gemcitabine only will be repeated on day 8 of the treatment cycle (i.e. one week after the two chemotherapy drugs are given together, the gemcitabine alone will be given). The study drugs will be administered through a vein in the patient's arm. The gemcitabine will be administered over 30 minutes, the cisplatin over 60 minutes. On chemotherapy days that include cisplatin (day 1 of each cycle) the patient will also receive fluids by vein. The procedure will take up to eight hours.
These fluids will be to keep the patient well hydrated and will consist of sterile salt water (saline solution) with extra minerals (potassium and magnesium) to help protect their kidneys from the chemotherapy. The patient may also receive a diuretic, a medication to help the kidneys remove this fluid from their body and protect the kidneys from damage. The patient will not need these on day 8 (gemcitabine alone).


If the patient is on Arm B:
The patient will receive the same chemotherapy as those on Arm A (i.e. one of the 3 regimens listed above) PLUS the addition of the drug bevacizumab (also given on the same day as day 1 of chemotherapy). Bevacizumab works by preventing the formation of new blood vessels, including those that surround and supply cancer cells, with the oxygen and nutrients they need to survive and grow. By taking away the blood supply, drugs like bevacizumab (also called angiogenesis inhibitors) may reduce tumor cell growth and cause cancerous tumors to grow more slowly or to become smaller. The bevacizumab will be infused over 30-90 minutes and repeated every three weeks. The bevacizumab
will continue beyond the chemotherapy for up to one year, or until evidence of tumor growth, or if the side effects from treatment are too severe to continue treatment.

- Bevacizumab will be given on day 1 of each 3-week cycle of chemotherapy for a total of four cycles, just after the chemotherapy, and will then continue to receive it for up
to one year, until disease progression, or complications from treatment. The initial dose will be administered over 90 minutes. If the patient does not experience any side effects, the next dose will be administered over 60 minutes. Again, if no side effects occur, the third and all remaining doses will be administered over 30 minutes.

The study drug (Bevacizumab) used in this study is considered investigational, which means it has either not been approved by the U.S. Food and Drug Administration (FDA) for routine clinical use or for the use described in this study. However the FDA has allowed the use of this drug in this research study.

Smoking Status Survey:
This study includes a survey asking whether or not the patient smokes, and if so, how much. The questionnaire regarding the patient's smoking habits is brief. The patient will take this survey before they begin study treatment, and every three months thereafter, for up to a year from study entry. On the same days the patient fills out their questionnaire, they may also be asked to take a urine dipstick test at their study doctor's office to verify their smoking status. This survey is being performed to determine what the relation is between smoking status and their disease and overall survival. The effect of gender on smoking status will also be examined.

How long will the Study run?

Patients will be in the study for about three months of chemotherapy treatment, up to one year of bevacizumab treatment (if they are randomized to arm B) and for six years of close followup to look for return of cancer. The research staff will keep track of the patient's medical condition for up to 10 years to look at the long-term effects of the study. The patient will also be asked about smoking at each of their follow-up visits. If a patient experiences any problems possibly related to treatment more than 10 years from study entry, those will also be reported.

Sponsor(s): Eastern Cancer Oncology Group (ECOG)

Study Activation/Registration Date: 03/05/2008

IRB Review and Approval Date: 02/01/2008

Study Type: Treatment

Projected Accrual: The plan is to have up to 1500 patients to 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, 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
• Jacksonville, FL

Last updated: 03/02/2009