IRB Number:

07-004011

Trial Status:

Open for Enrollment

Phase: II

Why is this study being done?

Patients are being asked to take part in this research study because they have breast cancer that has spread to other parts of their body. This research study is evaluating a drug called lapatinib as a possible treatment for breast cancer. In this study, the drug is combined with trastuzumab (Herceptin), which is a standard treatment for breast cancer. The FDA (the U.S. Food and Drug Administration) has not yet approved this drug combination for use for this type of cancer. Lapatinib is approved for use in this type of cancer when used in combination with capecitabine (Xeloda), a type of chemotherapy. Therefore, the use of the combination of Lapatinib and Herceptin is investigational. The purpose of this research study is to determine the effects that the combination of the study drug (lapatinib) plus Herceptin has on a patient and their cancer. Lapatinib is a compound that may stop cancer cells from growing.

This drug has been used in other research studies of patients with breast cancer and information from those research studies suggests that lapatinib in combination with Herceptin may help to shrink or stabilize breast cancer in this research study. In this research study, the staff are studying the effects of the combination of lapatinib plus Herceptin in patients with breast cancer that has spread outside of the breast. The researchers are also studying whether positron emission tomography (PET/CT) scans can predict which patients will benefit from the study treatment. Finally, the research staff are studying genes and proteins in the patient's tumor tissue that may lead to sensitivity or resistance to Herceptin and to the combination of Herceptin plus lapatinib. The researchers are also studying genes and proteins in the patient's tumor tissue to try to understand the changes that might occur to allow cancers to spread and/or to grow.

Who is Eligible to Participate in the Study?

-Age 18 or older
-Diagnosed with breast cancer that has spread to other parts of the body (metastatic)
-Prior hormonal therapy allowed

*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:

Before the research starts (screening): Patients will be asked to undergo some screening tests or procedures to find out if they can be in the research study. These tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that the patient does not take part in the research study. If the patient has had some of these tests or procedures recently, they may or may not have to be repeated.

- A medical history (questions about the patient's health, current medications, and any allergies).
- Physical examination (the research doctor will examine the patient's breathing, heart sounds, etc in the clinic)
- An assessment of the patient's tumor by CT (Computerized Tomography) scan and PET/CT (Positron Emission Tomography) scan. If the patient has a history of brain metastases, they will also have MRI (Magnetic Resonance Imaging) scan.
- Heart tests, including electrocardiogram (EKG) and heart scan (either MUGA scan or echocardiogram)
- Blood tests, including chemistry, hematology, and other tests to measure disease status, or to find out if a marker for this particular type of cancer exists. If the patient is a woman of childbearing potential, a pregnancy test will also be done.
- Urine test

If these tests show that the patient is eligible to participate in the research study, the research doctor will discuss the research biopsy with the patient. If the patient does not meet the eligibility criteria, they will not be able to participate in this research study.

If eligible and deciding to participate in this study, patients will be asked to undergo a biopsy (a procedure where a small amount of tissue is removed for analysis)
from an area of their body where your cancer has spread. The research doctor will tell the patient what area of their body will be biopsied (for example, skin, a lymph node, or liver). The research doctor, with the patient's input and consent, will select only one area to biopsy, even if the patient's breast cancer has spread to multiple areas. Before undergoing the biopsy, patients will discuss the specific procedure with the doctor who will perform the biopsy. This may be the research doctor, and/or a surgeon or
radiologist qualified to perform the procedure.

After patients have undergone the research biopsy: If taking part in this research study, patients will have the following tests and procedures:

Medication: If taking part in this research study, patients will be given a study medication dosing calendar for each treatment cycle. Each treatment cycle lasts four weeks during which time the patient will be taking the study drug, lapatinib, once per day. Patients will take their medication (tablets) by mouth, once a day in the morning.

Patients will receive Herceptin once every week through a vein. If they had Herceptin treatment within the past four weeks before the start of study treatment, the patient will be receiving Herceptin treatments over 30 minutes. If the patient did not have a Herceptin treatment within 4 weeks before the start of study treatment, then your first infusion will last for 90 minutes. After infusion, patients will be observed for 60 minutes to make sure that they do not have a reaction to Herceptin. If the first treatment went well, the patient's second treatment will last 30 minutes, followed by 30 minutes of observation. If the patient's second treatment went well, the rest of their Herceptin treatments will last 30 minutes with no observation period.

Physical Exams: During all treatment cycles patients will have a physical exam and they will be asked questions about their general health and specific questions about any problems that they might be having and any medications they may be taking.
Blood tests including chemistry, hematology, and other tests to measure any additional effect of the study drug and disease status, or if a marker for this particular type of cancer exists.

Photographs: Photographs may be taken of the patient's tumor to assess the response of the tumor to the treatment. Care will be taken to ensure these do not reveal the patient's identity.

PET/CT Scan: A second PET/CT scan will be performed one week after the patient's first dose of the study drug (lapatinib). This second scan is being done for research purposes. Patients will not be billed for the cost of the second scan. A third PET/CT scan will be performed in week 8. This scan will be billed to the patient's insurance company as standard of care.

CT scans: CT scans will be repeated every eight weeks to assess the effect of the study treatment on the patient's cancer.

MRI scans: If the patient's cancer has spread to their brain and they were treated, MRI scans will be done every 8 weeks to make sure the brain metastases are not growing bigger.

Heart scans (MUGA or echocardiogram): Either a MUGA scan or echocardiogram (measures of the strength of the heart pumping) will be performed eight weeks and 16
weeks after the patient starts the study treatment. If the patient's heart function remains stable, the scans will then be repeated every four months.

After the final treatment:

Physical Exams: Patients will have a physical exam and they will be asked questions about their general health and specific questions about any problems that they might be having and any medications they may be taking.

Photographs: Photographs may be taken of the patient's tumor to assess the response of their tumor to the treatment. Care will be taken to ensure these do not reveal the patient's identity.

How long will the Study run?

Patients will be in the study as long as they are benefiting from the study treatment. After finishing the study treatment, patients will be followed for up to 12 months.

Sponsor(s): Dana Farber

Study Activation/Registration Date: 02/29/2008

IRB Review and Approval Date: 10/26/2007

Study Type: Treatment

Projected Accrual: The plan is to have up to 85 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

Last updated: 07/11/2008