Study of Neoadjuvant Chemotherapy With Nanoparticle Albumin Bound Paclitaxel, Doxorubicin and Cyclophosphamide (NAC) in Patients With Stages II-III Breast Cancer

This is a single center, open phase I dose escalation study with expansion cohort. The dose
escalation part of the study is now closed and the highest tolerable dose of nab-paclitaxel
(Abraxane) was assessed to be 100 mg/m2 in combination with doxorubicin (Adriamycin) and
cyclophosphamide in patients with stages II-III breast cancer in the neoadjuvant setting.
The initial phase I study objective was to primarily assess the safety of the drug
combination, and to secondarily obtain preliminary data on the clinical efficacy of the
combination. 25 patients were enrolled. The expansion cohort will enroll 15 additional
patients.

The purpose of the expansion cohort is to assess pathological complete response.

Inclusion Criteria:

1. Histologically or cytologically proven adenocarcinoma of the breast stages II-III,
according to the AJCC Staging Manual, 7th Edition, 2009

2. The following receptor status:

Expansion: Triple negative (ER<1%, PR<1%, and Her-2/neu negative Phase 1 (closed):
Negative Her-2/neu status

3. ECOG performance status 0 or 1

4. Negative pregnancy test

5. Normal cardiac function (ejection fraction > lower limit of normal) as determined by
MUGA or echocardiogram

6. ANC greater than or equal to 1,500/mm3; platelet greater than or equal to
100,000/mm3; hemoglobin greater than or equal to 9 gm/dL

7. Serum bilirubin levels less than or equal to 1.5 mg/dL

8. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) less than or
equal to 2.5 X upper limit of normal, alkaline phosphatase less than or equal to 2.5
X upper limit of normal.

9. Serum creatinine levels less than or equal to 1.5 mg/dL

10. Women of childbearing potential should be advised to avoid becoming pregnant and men
should be advised to not father a child while receiving treatment with azacitidine or
nab-paclitaxel. Appropriate methods of birth controls for women include oral or
implanted contraceptives, intrauterine device (IUD), diaphragm with spermicide,
cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual
partner and also based on the judgment of the investigator.

11. Female, greater than or equal to 19 years of age and any race.

Exclusion Criteria:

1. Concurrent therapy with any other non-protocol anti-cancer therapy

2. Current therapy with hormone replacement therapy, or any hormonal agent such as
raloxifene, tamoxifen, or other selective estrogen receptor modulators

3. Presence of neuropathy > grade 2 (NCI-CTC version 3.0) at baseline

4. History of any other malignancy requiring active treatment

5. Clinically significant cardiovascular disease (e.g., hypertension [BP > 150/100],
myocardial infarction or stroke within 6 months, unstable angina), New York Heart
Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac
arrhythmia requiring medication

6. Currently active infection.

7. History of HIV infection or chronic hepatitis B or C.

8. The presence of any other medical or psychiatric disorder that, in the opinion of the
treating physician, would contraindicate the use of the drugs in this protocol or
place the subject at undue risk for treatment complications

9. Pregnancy or breast feeding

10. A history of a severe hypersensitivity reaction to nab-paclitaxel.

11. Any reason why, in the opinion of the investigator, the patient should not
participate.