IRB Number:

4-06

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

At the present time, researchers do not know if chemotherapy, for stage II colon cancer, can help reduce the chances that a patient's cancer might come back. Currently, the standard of care for individuals with this type of cancer is to receive no chemotherapy.

The research staff believe there may be biological features in the tumor (called tumor markers or markers) that will help to identify patients who should receive chemotherapy. The tumor markers to be used in this research study were selected based on experiments that showed they might identify patients who have a greater chance of having their cancer come back. The cancer researchers who designed this trial are trying to determine if patients with these tumor markers have a better chance of being cured if they receive chemotherapy after surgery. Therefore, the decision to give the patient chemotherapy will be made after the patient's tumor has been tested for the tumor markers. If those tumor markers suggest the patient may be at higher risk for the cancer coming back, the patient will get chemotherapy. However, if the tumor markers suggest the patient may be at a lower risk for the cancer coming back, the patient will not receive chemotherapy but they will be seen by their doctor with regularly scheduled visits.

This study is being done to:
- Determine whether specific biological features (often called tumor markers or markers) seen in tests done on a tumor (found in the colon) can be used to predict recurrence of tumors in patients with stage II colon cancer.
- Compare the effects (good and bad) of a combination of chemotherapy drugs, when given with and without a new drug, bevacizumab, on patients with stage II colon cancer at high-risk for recurrence.

The chemotherapy drugs given in this study are 5-fluorouracil (5-FU), leucovorin and oxaliplatin. The researchers want to see if adding bevacizumab to the other cancer-fighting agents is better for treating colon cancer patients, who may be at increased risk for recurrence based on the markers shown in their tumor. The research staff also want to see if adding bevacizumab will help prevent the cancer from coming back. The United States Food and Drug Administration (FDA) considers the use of bevacizumab to be investigational for treating Stage II colon cancer.

Who is Eligible to Participate in the Study?

-Age 18 or older
-Diagnosed with Stage 2 colon cancer
-No prior chemotherapy (systemic) or radiation therapy

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

What is Involved With this Study?

Before beginning this study, patients will need to have exams, tests or procedures. These tests are part of regular cancer care and may be done even if the patient does 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 the doctor.

- Biopsy of the tumor to evaluate two particular tumor markers, 18q LOH and microsatellite instability (MSI)
- Complete physical exam
- Blood and urine samples to evaluate the patient's health status
- Pregnancy test, if patient is female capable of bearing children
- Patients will need to keep a calendar of their aspirin use-if applicable

In addition, samples of the patient's tumor tissue will be forwarded to a designated laboratory and examined for tumor markers. This review will be used to determine whether they are assigned to the high-risk or the low-risk group.

During the study
If the marker evaluation of the patient's tumor shows that they may be at low-risk for tumor recurrence, then the patient will have regular follow-up office visits to monitor their health, but they will not receive any further treatment for the cancer, including chemotherapy.

If, however, the marker evaluation shows that the patient may be at high-risk for tumor recurrence, then they will be randomized into one of two study groups, Group A or Group B. Randomize means "to place into a group by chance". Neither the patient nor their doctor can choose the group the patient will be in. Patients will have an equal chance of being placed in one of the two groups.

Patients will receive treatment as described below.
- Patients will be seen by a doctor at the beginning of each cycle of treatment.
- Patients will have a complete physical exam and blood/urine samples will be obtained to evaluate their health status and to monitor treatment side effects throughout treatment. Approximately 3 teaspoons of blood will be drawn.

If the patient is in Group A, they will receive a standard 2-day regimen of chemotherapy, often referred to as FOLFOX (fluorouracil/leucovorin/oxaliplatin), given on Days 1 and 2, every two weeks for a total of 12, 2-week cycles. Medications are given before chemotherapy to prevent nausea and vomiting. All of the chemotherapy drugs will be given intravenously (through a vein). Oxaliplatin and leucovorin are given together over two hours, followed by 5-fluorouracil (5-FU) given as a quick infusion, followed by 5-FU given as a continuous infusion through a portable pump over the next 46 hours.

If the patient is in Group B, they will receive a standard 2-day regimen of chemotherapy, referred to as FOLFOX (fluorouracil/leucovorin/oxaliplatin), given on Days 1 and 2, every two weeks for a total of 12, 2-week cycles. The patient will also receive bevacizumab, on Day 1 every two weeks. After the first 12, 2-week cycles, they will receive bevacizumab alone for an additional 12, 2-week cycles, for a total time period of 24, 2-week cycles [one year]. Medications are given before chemotherapy to prevent nausea and vomiting. All of the drugs will be given intravenously (through a vein). Bevacizumab is given over 90 minutes, before the oxaliplatin, leucovorin and 5-FU. Oxaliplatin and leucovorin are given together over two hours, followed by 5-fluorouracil (5-FU) given as a quick infusion,
followed by 5-FU given as a continuous infusion through a portable pump over the next 46 hours.

Patients will require the placement of a temporary tube into a vein in their chest or their arm during the course of their treatment. This tube will be attached to a small portable pump. The drug, 5-FU, will be given using this pump. The pump is small enough to allow it to be attached to the patient's clothing, so it can be used without restricting most movements and activities. Patients will wear this pump for a 46-hour period.

Central Review
Samples of the patient's tumor tissue will be forwarded to a designated laboratory and examined. This review will be used to determine whether the patient is assigned to a high-risk or the low-risk group.

Six weeks after the patient has completed the treatment for Groups A and B, they will have the following routine tests which are part of standard follow-up care:

- Complete physical exam and blood tests will be obtained to evaluate the patient's health status and to monitor treatment side effects throughout that may have occurred since their last treatment. Approximately 5 teaspoons of blood will be drawn.

When finished with treatment (high-risk group) or if the patient is in the observation (low-risk group), they will have the following routine tests which are part of standard
follow-up care:

High-risk Group (Groups A & B):
- Routine physical exam and blood tests every three months for one-and-a-half years after completing FOLFOX or for one year after completing bevacizumab, then every six months for the next three years, then once a year for the next five years. Approximately, 1 teaspoon of blood will be drawn at each of the times the patient is seen.

Low-risk group (Arm C):
- Routine physical exam and blood tests every three months for two years, then every six months for the next three years, then once a year for the next five years. Approximately, 1 teaspoon of blood will be drawn at each of the times the patient is seen.

How long will the Study run?

If the patient is in Group A, they will receive FOLFOX for six months and will be followed for 10 years from start of treatment. If the patient is in Group B, they will receive FOLFOX plus bevacizumab for six months and then bevacizumab alone, for an additional six months for a total of one year of treatment. Group B patients will also be followed for 10 years from start of treatment. How long the patient will be in the study will depend on how they do with the drugs and how the cancer acts. Should the patient decide to stop taking the study drugs, their doctor will still want to keep in touch with the patient. If the patient was a low-risk patient, they will also be followed for 10 years.

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

Study Activation/Registration Date: 07/25/2007

IRB Review and Approval Date: 01/12/2006

Study Type: Treatment

Projected Accrual: The plan is to have up to 3610 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: Timothy J. Hobday, 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: 05/14/2008