IRB Number:

07-006349

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 early stage HER2 positive (HER2+) breast cancer that has been surgically removed. Patients will also have received some chemotherapy to treat the cancer. The most common treatment used in the United States and Canada is doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) - sometimes referred to as "AC," but it's possible the patient will have received another treatment.
The purpose of this research study is to:
- Find out what effects (good and bad) the study treatment has on the patient and their cancer.
- Compare four different study treatment combinations to see if one is better
- Find out what effects this study has on a patient's quality of life.

Because of recent research by North Central Cancer Treatment Group (NCCTG), the
standard treatment for HER2+ breast cancer now includes trastuzumab (Herceptin).
However, not all patients with HER2+ breast cancer do better with trastuzumab, so
investigators are trying to find out why.

GW572016 (lapatinib, brand name: Tykerb) is a new drug that is taken every day by mouth. Lapatinib is considered "investigational" in this study. "Investigational" means that the U.S. Food and Drug Administration (FDA) has not approved lapatinib as a treatment for early breast cancer.

This study is comparing trastuzumab to lapatinib and each drug alone to two
combinations of trastuzumab and lapatinib. The four treatments being studied here are:
- Group 1 - Standard treatment of trastuzumab alone for one year
- Group 2 - Lapatinib alone for one year
- Group 3 - Trastuzumab for 12 weeks followed by a six week break, and then
lapatinib for 34 weeks
- Group 4 - Trastuzumab and lapatinib together for one year
The true benefit of taking lapatinib either instead of trastuzumab or with trastuzumab is not known.

Who is Eligible to Participate in the Study?

- Age 18 or older
- Diagnosed with early stage HER2 positive (HER2+) breast cancer that has been surgically removed.
- Patient's tumor size is estimated to be ≥ 2 cm prior to surgery

What is Involved With this Study?

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

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 the patient does not join the study.
- Blood and/or urine tests
- Physical exam
- Chest x-ray or CT and mammogram
- Lab tests of your breast cancer tissue to see if it is HER2+
- Echocardiogram or MUGA scan to see how patient's heart is working
- Blood pregnancy test for women of child-bearing potential (able to become pregnant)
An echocardiogram looks at how the heart is working by tracing the electrical pattern the heartbeat makes. A MUGA scan is done by injecting a radioactive dye into a patient's bloodstream and watching their heart on an x-ray screen to see how well it is working.

Patients will be "randomized" into one of the study groups referenced below.
Randomization means that a patient is put into a group by chance (as in a roll of the dice). A computer program will place the patient in one of the study groups. Neither the patient nor their doctor can choose the group the patient will be in. A patient will have a one in four chance (25 percent) of being placed in any group. They will have a three in four chance (75 percent) of receiving lapatinib.

The drugs used in this study are considered investigational, which means they have either not been approved by the FDA for routine clinical use or for the use described in this study. However the FDA has allowed the use of the drugs in this research study.

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 the patient will need the following tests and procedures on a regular basis during this study. They are part of regular cancer care.
- Blood and/or urine tests
- Physical exams
- Echocardiogram or MUGA scan

Some patients will have finished chemotherapy before starting this study. Some patients in all groups will receive paclitaxel (Taxol) weekly for 3 months, which is standard of care for breast cancer patients in North America. If the doctor decides that the patient needs hormone therapy, it will be started after the patient finishes paclitaxel and will continue for at least five years. Also, if the doctor prescribes radiotherapy, it will be started after the patient is finished taking paclitaxel.

Paclitaxel (Taxol) and trastuzumab (Herceptin) are given intravenously, that is, through a needle into a vein in the arm or hand, or into a port if the patient has one. If in Groups 1, 3 or 4, the patient will receive both paclitaxel and trastuzumab once a week for 12 weeks. Groups 1 and 4 will then receive trastuzumab once every three weeks until they have received one year of treatment.

If in Group 3, the patient will receive trastuzumab once every week for 12 weeks, and then will then have a break for six weeks. After the break the patient will start taking lapatinib every day until they have received one year of treatment.
Lapatinib (Tykerb) comes in tablets that are taken by mouth. The patient will take lapatinib every day for one year. The patient will get a new supply of lapatinib from their clinic about every three months.

When finished taking the study drugs,
The research staff will follow the patient's progress for five years after starting the study. After the patient has completed treatment, they will come to the clinic every three months through Year 2, then every six months until they've been in the study for five years. The patient will then come to the clinic once a year until they have been in the study for 10 years.

How long will the Study run?

Patients will be in this study for up to 14 years. They will receive the study treatment for one year. After finished taking the study drugs, the study doctor will ask the patient to visit the office for follow-up study exams every three months until two years after they started the study, then every six months until five years from when they started the study. Then, the research staff would like to keep track of the patient's health every year for up to 14 years after the patient started the study.

Sponsor(s): Glaxo Smith Kline, North Central Cancer Treatment Group (NCCTG), Breast International Group (BIG)

Study Activation/Registration Date: 15 February 2008

IRB Review and Approval Date: 30 November 2007

Study Type: Treatment

Projected Accrual: The plan is to have up to 8000 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: 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
• Scottsdale and Phoenix, AZ

Last updated: 05/07/2008