Cyclophosphamide, Paclitaxel, and Trastuzumab in Treating Patients With Stage I-II HER2/Neu Positive Breast Cancer After Surgery

PRIMARY OBJECTIVES:

I. To determine the toxicities and ability to complete the planned treatment of a dose-dense
regimen of cyclophosphamide and paclitaxel with trastuzumab in subjects with newly diagnosed
stage I-II HER2/neu positive breast cancer.

II. To estimate recurrence free survival of a dose-dense regimen of cyclophosphamide and
paclitaxel with trastuzumab in subjects with newly diagnosed stage I-II HER2/neu positive
breast cancer.

OUTLINE:

SYSTEMIC THERAPY: Patients receive cyclophosphamide intravenously (IV) over 1 hour,
paclitaxel IV over 3 hours, and trastuzumab IV over 30-90 minutes on day 1. Treatment repeats
every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE TRASTUZUMAB THERAPY: Beginning in course 6, patients receive trastuzumab IV over
30-60 minutes on day 1. Treatment repeats every 21 days for up to 52 weeks in the absence of
disease progression or unacceptable toxicity.

Patients may undergo radiation therapy at the discretion of the radiation oncologist and
medical oncologist and patients with estrogen/progesterone receptor positive tumors receive
hormonal therapy as determined by the medical oncologist per standard National Comprehensive
Care Network (NCCN) guidelines.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Inclusion Criteria:

- Histologically confirmed newly diagnosed stage I-II HER2/neu positive breast cancer

- Women of reproductive potential must be non-pregnant and non-nursing and must agree to
employ an effective barrier method of birth control throughout the study and for up to
6 months following treatment

- Women of child-bearing potential must have a negative pregnancy test within 7 days of
initiating study (no childbearing potential is defined as age 55 years or older and no
menses for two years or any age with surgical removal of the uterus and/or both
ovaries)

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Within 30 days prior to enrollment: Absolute neutrophil count greater than or equal to
1,500/mcl

- Within 30 days prior to enrollment: Platelet count equal to or greater than
150,000/mcl

- Within 30 days prior to enrollment: Hemoglobin > 11 gm/dl

- Within 30 days prior to enrollment: Alkaline phosphatase equal or less than 1.5 times
the upper limit of normal (ULN)

- Within 30 days prior to enrollment: Total bilirubin equal to or less than 1.5 times
the ULN

- Within 30 days prior to enrollment: Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) no greater than 1.5 times the ULN

- Within 30 days prior to enrollment: Creatinine less than 1.5 times the ULN

- Able to give informed consent

- All included subjects must have normal cardiac function as defined by an ejection
fraction of > 50% by echocardiogram

- Able to return for treatment and follow-up on the specified days

Exclusion Criteria:

- Prior malignancy; except for adequately treated basal cell or squamous cell skin
cancer or noninvasive carcinomas

- Subjects with pre-existing grade II peripheral neuropathy

- History of previous chemotherapy

- Stage IV or metastatic breast cancer

- Pregnant or nursing women

- Inability to cooperate with treatment protocol

- No active serious infections or other conditions precluding chemotherapy

- Any comorbidity or condition which, in the opinion of the investigator, may interfere
with the assessments and procedures of this protocol e.g. unstable angina, myocardial
infarction within 6 months, severe infection, etc.

- Known hypersensitivity to any component of required drugs in the study

- Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A,
B or C or active hepatitis

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form

- Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) class III or IV heart failure uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities; prior to study entry, any
electrocardiographic (ECG) abnormality at screening has to be documented by the
investigator as not medically relevant