IRB Number:

07-005451

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

The purpose of this study is to find out if the addition of bevacizumab improves response and survival.

Bevacizumab is the common name for the commercial drug Avastin. The bevacizumab used in this trial, however, is for use in research studies only and may be made at locations different from those where Avastin is made. Although some differences may exist, bevacizumab for research use and the commercial drug, Avastin, are manufactured by a similar process, meet similar standards for final product testing, and are expected to be very similar in safety and effectiveness.

Who is Eligible to Participate in the Study?

-Age 18 or older
-Diagnosed with colorectal cancer that has spread and that has not responded to prior treatment that included bevacizumab.
-No prior treatment with irinotecan

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

What is Involved With this Study?

If patients agree to be in the study, they will be asked to participate in the following:

Treatment Plan
Patients will either receive irinotecan by itself or FOLFIRI, which is a combination of drugs including irinotecan. It is up to the patient and their study doctor whether they receive irinotecan or FOLFIRI. If their doctor suggests irinotecan by itself, this will be given to the patient every 3 weeks by an IV (into their vein) over 90 minutes.

If their doctor chooses FOLFIRI, this will be given to the patient every 2 weeks. FOLFIRI includes the following drugs: irinotecan (IV for 90 minutes), then leucovorin (IV for 2 hours), then a 2-4 minute injection of 5-FU, then 5-FU (IV for 46-48 hours). The 46-48 hours of 5-FU will be a continuous IV infusion given through an outpatient infusion pump.

In addition to receiving irinotecan or FOLFIRI, patients will be "randomized" into one of the study groups described below. Randomization means that patients are put into a group by chance (as in the flip of a coin). A computer program will place the patient in one of the study groups. Neither the patient nor their doctor can choose the group they will be in. Patients will have a one in three chance of being placed in any group. The patient will be told what group they are in.

GROUP 1
If patients are in Group 1 (often called "Arm 1"), they will receive cetuximab weekly. When it is given on the same day as irinotecan or FOLFIRI it will be given first. This will be given to the patient by IV. The first time the cetuximab is given, it will take 2 hours. After that, it will only take 1 hour.

GROUPS 2 and 3
If patients are in Group 2 or Group 3, they will receive cetuximab weekly. When it is given on the same day as irinotecan or FOLFIRI, it will be given first. This will be given to the patient by IV. The first time the cetuximab is given, it will take 2 hours. After that, it will only take 1 hour. Patients will also receive bevacizumab. If they are receiving irinotecan, bevacizumab will be given every 3 weeks (right after the cetuximab). If they are receiving FOLFIRI, bevacizumab will be given every 2 weeks. The bevacizumab IV takes 30 minutes, but if the patient had previous problems with a bevacizumab infusion, their IV may take longer.

The only difference between Groups 2 and 3 is that Group 3 will receive a higher dose of bevacizumab than Group 2.

Before beginning the study
Patients will need to have the following exams, tests or procedures to find out if they can be in the study. These exams, tests or procedures are part of regular cancer care and may be done even if they do not join the study. If the patient has had some of them recently, they may not need to be repeated. This will be up to their study doctor. These tests will all be performed in an outpatient setting.

- Physical exam
- Blood pressure
- X-rays and scans
- Blood tests for blood counts, clotting time, and kidney and liver function
- Urine tests for kidney function
- Pregnancy test (women able to become pregnant)

During the study
If the exams, tests and procedures show that the patient can be in the study, and they choose to take part, then they may need the following tests and procedures. They are part of regular cancer care. These tests will all be performed in an outpatient setting.

- Physical exam every three weeks
- Blood pressure every three weeks
- X-rays and scans every six weeks
- Blood tests every three weeks
- Urine tests before every other treatment with bevacizumab

After patients are finished taking the study drugs, they will have follow-up visits with the study doctor for up to three years from the time they started the study. If their disease did not get worse while they were on the study drugs, the patient will continue to have scans every six weeks during this time. Otherwise, they will see the doctor every six months for lab tests and a physical exam.

The drug 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.

How long will the Study run?

Patients will continue taking the study drugs as long as their disease does not get worse and the side effects are not too bad. After they are finished taking the study
drugs, the study doctor will ask the patient to visit the office for follow-up exams for up to 3 years.

Sponsor(s): Southwest Oncology Group (SWOG)

Study Activation/Registration Date: 10/31/2007

IRB Review and Approval Date: 10/03/2007

Study Type: Treatment

Projected Accrual: The plan is to have up to 1260 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: Axel Grothey, 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: 05/20/2009