IRB Number:

06-003281

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

This study is being done to:
- Determine whether patients who have a tumor with a 10 percent chance of their tumor
recurring (coming back following treatment) after 10 years benefit from
chemotherapy
- Determine whether patients who have a 5 percent chance of their tumor recurring
(coming back following treatment) after 10 years have a very low risk of recurrence with hormonal therapy alone (and do not need chemotherapy to reduce their risk of recurrence)
- Create a tissue and blood specimen bank that includes specimens from all women who participate in this study
- Collect follow-up information regarding the health status of all women who
participate in the study for 20 years in order to evaluate new diagnostic tests in the
future as they develop that may predict benefit or side effects from certain cancer
treatments.
Patients are being asked to take part in this trial because they have breast cancer that is estrogen receptor and/or progesterone receptor positive that has not spread to the auxiliary lymph nodes. Although the patients have received surgical treatment for their cancer, there is a chance that they may have a future recurrence of the cancer in the breast, chest wall, or other parts of their body. Based on researchers' current knowledge about the treatment of breast cancer, the doctors believe that patients in this study are candidates for chemotherapy in addition to hormonal therapy in order to reduce their risk of recurrence, a recommendation that is consistent with established guidelines for treatment of this type of breast cancer.

Who is Eligible to Participate in the Study?

-Women with estrogen and/or progesterone positive and HER2/neu negative expressing tumor, without spread to the axillary lymph nodes
-No prior chemotherapy or radiation for this cancer.


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

What is Involved With this Study?

This study involves the use of a new diagnostic test called the Oncotype DX (Genomic Health, Inc, Redwood, California). This test involves analysis of cancer tissue that has already been taken during the patient's surgery and has been stored in the pathology laboratory affiliated with the facility where they had the surgery. Storage of the cancer in the pathology laboratory after surgery is a routine procedure. The analysis requires that several small slices of the tumor section be taken. The sections will be analyzed in a specialized laboratory that can measure the levels of a specific panel of genes in the tumor. The laboratory that performs this test (Genomic Health Laboratory) has been certified by federal and state agencies in the United States to perform the test (Oncotype DX). The results of the test are computed into a score (called Recurrence Score). The results from initial studies indicate that tumors may be classified into the following groups:

- Secondary Study Group-1 (Recurrence Score less than 10): This group has a 5 percent or less chance of having a relapse of breast cancer in other organs at 10 years if treated with hormonal therapy alone. In this group, chemotherapy has not been proven to reduce the risk of recurrence. Approximately 25 percent of patients have a tumor with a Recurrence Score of less than 10.
- Primary Study Group (Recurrence Score 11-25): This group has about a 10 percent chance of having a relapse of breast cancer in other organs at 10 years if treated with hormonal therapy. In this group, although the risk of recurrence is high enough to recommend consideration of chemotherapy, it is unknown whether chemotherapy reduces the risk of recurrence and whether the overall health benefits favor the use of chemotherapy. About 40 percent of patients have a tumor with a Recurrence Score of 11-25.
- Secondary Study Group-2 (Recurrence Score greater than 26): This group has about a 30 percent chance of having a relapse of breast cancer in other organs at 10 years if treated with hormonal therapy. In this group, chemotherapy reduced the risk of recurrence by about 75 percent. In other words, adding chemotherapy increases the chance of being without disease recurrence at 10 years from about 70 percent to about 90 percent in this group. About 35 percent of patients have a tumor with a Recurrence Score of greater than 26.

If a patient agrees to participate in this study, the sequence of events is described below. If they have not had the Oncotype DX test performed, a tumor specimen will be sent to Genomic Health for the Oncotype DX test. It will take about 10 to 14 days to obtain the results of the test back from Genomic Health. The results will be sent to the patient's study doctor. The Oncotype DX test that is being done as part of this study is not a research test. A copy of the Oncotype DX test report will be placed in the patients medical record. The study doctor will fax the report to the ECOG (Eastern Cooperative Oncology Group) Coordinating Center, the Center coordinating the study. Genomic Health will also send to the ECOG Coordinating Center detailed results outlining how they determined the patient's Recurrence Score and additional information describing the tissue samples sent to them.

This information will not be sent to the patient or their study doctor or their insurance company. It will not be placed in their medical record. It will only be used for research to help better understand breast cancer. One to three days after the report has been sent to the ECOG Coordinating Center, the patient will proceed to the next phase of the study, and specific treatments will be recommended:

- Secondary Study Group-1 (Recurrence Score less than 10): Patients will receive hormonal therapy, but no chemotherapy (Treatment Group A).
- Secondary Study Group-2 (Recurrence Score greater than 26): Patients will receive
chemotherapy plus hormonal therapy (Treatment Group D).
- Primary Study Group (Recurrence Score 11-25): Patients will be randomly assigned by chance (like a coin flip) to treatment with either:
- hormonal therapy alone (Treatment Group B)
- chemotherapy plus hormonal therapy (Treatment Group C)

If patients have already had the Oncotype DX test performed, they may be eligible for this trial if their Recurrence Score was 11-25. If this is the case, their study doctor will fax a copy of the Recurrence Score report to the ECOG Coordinating Center. The patient will then be randomly assigned by chance (like a coin flip) to receive either hormonal therapy (Treatment Group B), or chemotherapy followed by hormonal therapy (Treatment Group C).

Before a patient begins the study treatment, they 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 these tests or procedures recently as part of their regular care, they may not need to be repeated. The study doctor will let the patient know which tests are needed to determine if they are able to take part in this study. These test and procedures may include:
- History and physical examination
- Blood tests (including complete blood count and liver and kidney function tests)
- Mammogram
- Serum pregnancy test if woman able to become pregnant
- Oncotype DX test, if this was not previously done

During and after the treatment
Patients will then receive treatment with chemotherapy and/or hormonal therapy in accordance with standard care according to their treatment group assignment.
When chemotherapy is given, it is usually administered over three to six months. Hormonal therapy is usually given for five years or longer, and begins after the completion of chemotherapy (if given).

Patients will need the following tests and procedures during and after treatment in order to determine if there is a relapse of the breast cancer, or if another breast cancer develops. These procedures/tests are part of regular cancer care, and include the following:
- History and physical exam every three to six months for the first five years, then yearly after year 5
- Mammogram once yearly

There are several different types of chemotherapy and hormonal therapy, which the study doctor will discuss with the patient. In addition to this trial, their study doctor may offer the patient participation in another clinical trial that is testing different types of chemotherapy and/or hormonal therapy and/or radiation therapy.

Patients who have had a lumpectomy will also be treated with radiotherapy after chemotherapy is completed. If the patient has been randomized or assigned to hormonal therapy alone, it will begin within 14 days of study registration/randomization. If the patient has been randomized or assigned to chemotherapy, it will also begin within 14 days after study registration/randomization. After chemotherapy is completed, hormonal therapy will begin within four weeks after the last dose of chemotherapy. Treatment with hormonal therapy will be given at the same time as radiation therapy.

The study doctor will monitor the patient periodically for recurrence of the cancer, which is part of routine medical care. Once the patient has been in the study for more than five years, the research staff will continue to collect information on the patient's yearly exam and send the results to ECOG for 15 more years. The patient will have a history and physical exam along with a mammogram yearly.

How long will the Study run?

Patients will be in the study for 20 years.

Sponsor(s): Eastern Cooperative Oncology Group (ECOG), National Cancer Institute (NCI)

Study Activation/Registration Date: 10/12/2007

IRB Review and Approval Date: 10/10/2007

Study Type: Treatment

Projected Accrual: The plan is to enroll up to 11, 000 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: Edith Perez, 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: 06/27/2008