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TBCRC 023: A Randomized Multicenter Phase II Neoadjuvant Trial of Lapatinib Pus Trastuzumab, With or Without Endocrine Therapy for 12 Weeks vs. 24 Weeks in Patients With HER2 Overexpressing Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

TBCRC 023: A Randomized Multicenter Phase II Neoadjuvant Trial of Lapatinib Pus Trastuzumab, With or Without Endocrine Therapy for 12 Weeks vs. 24 Weeks in Patients With HER2 Overexpressing Breast Cancer

Breast cancer cells have certain characteristics or traits--these traits are called
biomarkers. There are three biomarkers that help doctors decide which treatment to give any
given patient. These biomarkers are the estrogen receptor (ER), progesterone receptor (PgR),
and HER2 protein. Breast cancer cells that have a large number of estrogen or progesterone
receptors are called ER and/or PgR positive. Cancers that are ER and/or PgR positive use the
hormones estrogen and progesterone to help them grow. Not all breast cancers are ER or PgR
positive. Patients are being asked to take part in this study that have a special type of
breast cancer called HER2 positive breast cancer. HER2-positive breast cancer is a breast
cancer that tests positive for a protein called human epidermal growth factor receptor-2
(HER2). HER2 is located on the outer surface of a cancer cell. The HER2 protein sends a
signal to the inside of the cancer cells telling it to grow and divide.

Two medications that directly target this HER2 protein. One is called
trastuzumab(Herceptin), and the other is called lapatinib (Tykerb). Both medications are
FDA-approved for the treatment of women with HER2+ breast cancer. Each medication attaches
to the protein so that it can no longer function. Once the protein stops working, the cancer
cells can no longer make copies of themselves. This makes cancer shrink. Both drugs target
HER2; however each drug works a little bit differently.

Some patients respond better to Herceptin, and some patients respond better to Tykerb. Right
now, we are not sure why some patients respond to one drug but do not respond to the other
drug. One possibility is that in some patients, the HER2 protein finds another way to send
its message to the inside of the cell (similar to a road detour). For example, when one path
is "closed" because the drug is blocking it, the HER2 protein finds a different way to send
its signal. We think that we can completely block the HER2 protein by giving patients both
Tykerb and Herceptin.

Some patients with HER positive breast cancer are also ER and/or PgR positive. Even after
HER2 is completely blocked, these types of cancer cells can still grow by using the estrogen
or progesterone receptor. If a patient is told they are ER and/or PgR positive, they will
also take an anti-estrogen pill along with Tykerb and Herceptin. We think that we can stop
cancer growth more completely by blocking both the HER2 protein and the ER/PR receptors.

Inclusion Criteria:

1. All patients must be female and at least 18 years of age.

2. Signed informed consent.

3. Locally advanced breast cancers are eligible. Locally advanced cancers must be of
clinical and/or radiologic size >3 cm, or >2 cm with clinical evidence of axillary
nodal involvement*. (If tumors are less than 3 cm, we will use the radiologically
measured tumor size to determine if the tumor meets the minimal size requirements.)

4. Patients must have histologically confirmed invasive mammary carcinoma that is HER2
overexpressing, defined as 3+ by immunohistochemistry, or a FISH/CEP ratio greater
than 2.

5. Negative serum pregnancy test (HCG) within 7 days of starting study drug, if of
child-bearing potential.

6. Kidney and liver function tests - all within 1.5 times the institutional upper limit
of normal.

7. Performance status (WHO/ECOG scale) 0-1 and life expectancy >6 months.

8. No evidence of brain or leptomeningeal disease, or any other Stage IV disease.

9. No previous or current malignancies at other sites within the last 5 years, with
exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri
and basal or squamous cell carcinoma of the skin.

Exclusion Criteria:

1. Patients with bilateral breast cancer.

2. Pregnancy or unwillingness to use a reliable contraceptive method in women of
child-bearing potential.

3. Severe underlying chronic illness or disease.

4. Cardiomyopathy or baseline LVEF less than 50%.

5. Other investigational drugs while on study.

6. Severe or uncontrolled hypertension, history of congestive heart failure or severe
coronary arterial disease.

7. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel. Subjects with ulcerative colitis are also

8. Taking any lapatinib prohibited medication(s)

9. Inability or unwillingness to comply with, or follow study procedures.

10. Patients who have received any form of treatment for breast cancer within the past
five years, including surgical resection, chemotherapy, endocrine therapy, or
biologic therapy.

11. Patients with a prior history of ipsilateral invasive breast cancer or carcinoma in
situ who present with a new primary.

12. Patients with known active, infectious Hepatitis B, Hepatitis C, or HIV.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the rate of pathologic complete response, defined as no residual invasive cancer in the breast, after 12 or 24 weeks of lapatinib/trastuzumab with or without endocrine therapy.

Outcome Description:

We propose a randomized multicenter neoadjuvant clinical trial in HER-2 overexpressing breast cancer patients with 12 vs. 24 weeks of lapatinib plus trastuzumab, with or without endocrine therapy, during which serial cancer tissue samples will be obtained for molecular studies in relation to tumor response. The patients will receive either 12 or 24 weeks of therapy to determine the pathologic complete response rate to this combined targeted therapy regimen, without the addition of any cytotoxic chemotherapy.

Outcome Time Frame:

5 years

Safety Issue:


Principal Investigator

Mothaffar Rimawi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine


United States: Food and Drug Administration

Study ID:




Start Date:

October 2011

Completion Date:

January 2018

Related Keywords:

  • Breast Cancer
  • Locally Advanced Breast Cancer Neoadjuvant Endocrine
  • Breast Neoplasms



Vanderbilt University Medical CenterNashville, Tennessee  37232-2516
Duke UniversityDurham, North Carolina  27710
Dana Farber Cancer InstituteBoston, Massachusetts  02115
University of ChicagoChicago, Illinois  60637
Indiana UniversityIndianapolis, Indiana  46202
Johns HopkinsBaltimore, Maryland  21231
University of Alabama - BirminghamBirmingham, Alabama  35294
Baylor College of Medicine Lester and Sue Smith Breast CenterHouston, Texas  77030