Phase III Trial of TC Versus TAC in HER2-Negative Early Stage Breast Cancer Patients

Inclusion Criteria:

A woman will be eligible for inclusion in this study if she meets all of the following
criteria:

- Age >18 to <70 years old.

- Has known ER and PR status

- Has HER2 nonamplified disease, confirmed by FISH

- Has known menopausal status (see Section 7.3 for criteria)

- Has operable, histologically confirmed, Stage I, IIA, IIB, or IIIA, IIIB, or IIIC
invasive carcinoma of the breast. Bilateral synchronous breast cancer is allowable
provided that 1 primary meets the inclusion criteria.

- Meets 1 of the 3 following criteria:

- T1-3N1-3M0 if ER positive or negative

- T2-3N0M0 if ER positive or negative

- T1N0M0 if ER and PR negative

- Has complete surgical resection of the primary breast tumor: either lumpectomy or
mastectomy with sentinel lymph node biopsy or axillary dissection, with clear margins
for both invasive and ductal carcinoma in situ (DCIS)

- Has had no prior chemotherapy unless >5 years ago

- Has an ECOG Performance Status (PS) 0-1

- Has laboratory values of: See protocol for specific details

- Has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline
phosphatase (ALP) within the ranges shown below. In determining eligibility the more
abnormal of the 2 values (AST or ALT) should be used. See protocol for specific
details

- Has normal cardiac function as evidenced by a LVEF >50%, but WNL by institutional
standard by multiple gated acquisition (MUGA) scan. An echocardiogram (ECHO) may be
used if MUGA is not available, but the same modality must be used consistently
throughout the study to evaluate LVEF. Ejection fraction as determined by ECHO must
be WNL by institutional standard.

- Has no evidence of metastatic disease outside of breast by physical examination and
chest x-ray. Other scans if done as needed by the patient (eg, bone scan; abdominal,
chest CT; PET or PET/CT; ultrasound; or MRI should indicate no evidence of metastatic
disease

- Has had baseline bilateral mammography

- It has been <84 days since the date of definitive surgery (eg, mastectomy or, in the
case of a breast-sparing procedure, axillary dissection) with adequate wound healing,
as determined by the Treating Physician

- Has a negative serum pregnancy test within 7 calendar days prior to registration
(female patients of childbearing potential [not surgically sterilized and between
menarche and 1 year postmenopause])

- If fertile, patient has agreed to use an acceptable method of birth control (barrier
contraceptive only) to avoid pregnancy for the duration of the study and for a period
of 3 months thereafter

- Has adequate tumor specimen available for FISH analysis of TOP2A status (See Appendix
VI).

- Has signed a Patient Informed Consent Form

- Has signed a Patient Authorization Form

Exclusion Criteria:

A woman will be excluded from this study if she meets any of the following criteria:

- Has any evidence of metastatic disease following surgical resection of the primary
tumor including: positive surgical margins, staging work-up, or physical examination
suspicious for malignant disease

- Has T4 disease (ie, patients with fixed tumors, peau d'orange skin changes, skin
ulcerations, or inflammatory changes)

- Has Stage IV breast cancer (M1 disease on TNM staging system)

- Has a history of severe hypersensitivity reaction to drugs formulated with
polysorbate 80

- Has had neoadjuvant chemotherapy for this breast cancer

- Has ever had a myocardial infarction (MI) or has a history of heart failure,
uncontrolled angina, severe uncontrolled arrhythmias, pericardial disease, or
electrocardiographic evidence of acute ischemic changes

- Is receiving concurrent immunotherapy, hormonal therapy (eg, tamoxifen, hormone
replacement therapy), or radiation therapy. Must discontinue prior to registering on
the study.

- Is receiving concurrent investigational therapy or has received such therapy within
the past 30 calendar days

- Has peripheral neuropathy >Grade 1

- Has had a major organ allograft or condition requiring chronic immunosuppression (ie,
kidney, liver, lung, heart, bone marrow transplant, or autoimmune diseases). Patients
who have received corneal transplants or cadaver skin or bone transplants are
eligible.

- Has a serious uncontrolled intercurrent medical or psychiatric illness, including
serious viral (including clinically defined AIDS), bacterial or fungal infection; or
history of uncontrolled seizures, or diabetes, or CNS disorders deemed by the
Treating Physician to be clinically significant, precluding informed consent

- Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is
known to be HIV positive

- Has a history of other malignancy within the last 5 years (except cured basal cell
carcinoma of skin, carcinoma in situ of uterine cervix, DCIS, which could affect the
diagnosis or assessment of any of the study drugs

- In an obese patient to whom the Treating Physician would not be comfortable
administering full doses of study drugs as calculated by the BSA. Obese patients will
be treated based on actual body weight. Obese patients treated with full doses based
on actual BSA are eligible.

- Is pregnant or breastfeeding

- Is deemed unable to comply with requirements of study