Carboplatin and Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IIB-IIIC Breast Cancer

PRIMARY OBJECTIVE:

1) To compare the pathologic complete response (path CR) in patients with stage IIB or stage
III triple negative breast cancer treated with neoadjuvant paclitaxel and carboplatin to the
path CR of patients treated with paclitaxel, carboplatin, and veliparib.

SECONDARY OBJECTIVES:

1. Relapse free survival (follow-up period of 36 months).

2. Overall clinical response to neoadjuvant therapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) and carboplatin IV on day 1 (course 1
only) or day 2 (courses 2-12). Treatment repeats every 7 days for 12 courses in the absence
of disease progression or unacceptable toxicity. Beginning 21 days after the last course,
patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1. Treatment
repeats every 21 days for 4 courses in the absence of disease progression or unacceptable
toxicity.

ARM II: Patients receive veliparib orally (PO) twice daily (BID) on days 1-5. Patients also
receive paclitaxel IV and carboplatin IV on day 3 (course 1 only) or day 4 (courses 2-12).
Treatment repeats every 7 days for 12 courses in the absence of disease progression or
unacceptable toxicity. Beginning 21 days after the last course, patients receive doxorubicin
hydrochloride IV and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4
courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 36 months.

Inclusion Criteria:

1. Written informed consent must be obtained prior to any study-related procedures.

2. Histologically confirmed adenocarcinoma of the breast with the following markers:
Estrogen receptor negative (<1%), progesterone receptor negative (<1%), and Her-2/neu
negative (Her-2/neu 0-1+ IHC or FISH ratio <1.8 or average HER2 gene copy number of

3. Female ≥ 18 years old.

4. Clinical stage IIA (T2N0), IIB (T2N1, T3N0) or stage IIIA (T1N2, T2N2, T3N1, T3N2),
IIIB, or IIIC breast cancer with no prior treatment.

5. Complete radiology or tumor assessment within 28 days prior to enrollment

1. Breast MRI

2. Unilateral Breast Ultrasound

3. Distant metastatic work-up completed with PET/CT.

4. If enlarged axillary lymph nodes are found during staging scans, FNA must be
performed to determine whether the node is involved with cancer.

5. If axillary lymph nodes are clinically negative during initial work-up, sentinel
node biopsy will be performed prior to initiation of chemotherapy.

6. ECOG Performance Status of 0 or 1

7. Adequate organ and hematologic function as evidenced by the following laboratory
studies within 4 weeks of study enrollment:

1. Cardiac Ejection Fraction >/= lower limit of normal as determined by 2-D echo or
MUGA scan according to institutional standards.

2. Hematologic function, as follows: Absolute neutrophil count ≥ 1.5 x 109/L,
Platelet count ≥ 100 x 109/L and ≤ 850 x 109/L, Hemoglobin ≥ 9 g/dL, PTT and INR
< 1.5 x ULN.

3. Renal function, as follows: Serum creatinine
4. Hepatic function, as follows:Aspartate aminotransferase (AST) ≤ 2.5 x ULN,
Alanine aminotransferase (ALT) ≤ 2.5 x ULN , Total bilirubin ≤ 2 x ULN (except
for patients with UGT1A1 promoter polymorphism, i.e. Gilbert syndrome, confirmed
by genotyping or Invader UGT1A1 molecular assay prior to study enrollment.
Patients enrolled with Gilbert syndrome must have total bilirubin < 3 ULN).

8. Patient must be willing and able to undergo MRI as outlined in protocol.

Exclusion Criteria:

1. Known hypersensitivity to doxorubicin, cyclophosphamide, paclitaxel, cremophor or
medications containing cremophor(miconazole, docetaxel, sandimmune, nelfinavir
mesylate, propofol, diazepam injection, vitamin K injection, ixabepilone, aci-jel) or
carboplatin.

2. Known HIV or active Hepatitis B or C infection.

3. Prior treatment for the currently diagnosed breast cancer.

4. Prior treatment with doxorubicin up to 400 mg/m2.

5. Pre-existing Grade 3 or 4 sensory neuropathy.

6. History of bleeding diathesis or extensive bleeding requiring blood transfusion within
14 days of enrollment.

7. Major surgical procedure within 4 weeks (28 days) prior to enrollment (port placement
is not considered a major surgical procedure).

8. Clinically significant cardiac disease within 12 months of study enrollment, including
myocardial infarction, unstable angina, congestive heart failure, or ongoing
arrhythmias requiring medication or pacemaker.

9. Non-healing wound, ulcer or fracture.

10. Ongoing or active infection.

11. Pregnant (i.e., positive beta-human chorionic gonadotropin test) or lactating

12. Not willing to use a highly effective method of birth control (i.e. those which result
in low failure rates, less than 1% per year), defined as intrauterine devices, barrier
methods (condoms, contraceptive sponges, diaphragms, vaginal rings used with
spermicidal jellies or creams), oral contraceptive pills, or sexual abstinence.
Contraception must be used during the study.

13. T0 tumors

14. Active dental infection