Cyclophosphamide and Paclitaxel With or Without Trastuzumab in Stage I-II Breast Cancer Who Have Undergone 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 or without trastuzumab in patients with newly
diagnosed stage I-II breast cancer.

II. To estimate recurrence free survival of a dose-dense regimen of cyclophosphamide and
paclitaxel with or without trastuzumab in patients with newly diagnosed stage I-II breast
cancer.

OUTLINE:

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

MAINTENANCE THERAPY (human epidermal growth factor receptor 2 [Her-2] neu positive patients):
Patients receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for
5 courses and then every 21 days for 14 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 3 years.

Inclusion Criteria:

- Histologically confirmed newly diagnosed stage I-II 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

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

- Absolute neutrophil count greater than or equal to 1,500/mcl

- Platelet count equal to or greater than 150,000/mcl

- Hemoglobin > 11 gm/dl

- Alkaline phosphatase equal or less than 1.5 times the upper limit of normal (ULN)

- Total bilirubin equal to or less than 1.5 times the ULN

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than
1.5 times the ULN

- Creatinine less than 1.5 times the ULN

- Able to give informed consent

- All included patients 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

- Patients with preexisting grade II peripheral neuropathy

- Patients with prior 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
electrocardiograph (ECG) abnormality at screening has to be documented by the
investigator as not medically relevant