Sequential Phase I - Randomized Phase II, Double-Blind, Placebo-Controlled Trial of Cyclophosphamide Alone or in Combination With Veliparib (ABT-888) in ER and/or PR-Positive and HER2/Neu-Negative Metastatic Breast Cancer

Inclusion Criteria:

- Phase I: Patients must have histologically confirmed breast cancer (MBC) that is
HER2/neu negative (as determined by local pathology or reference laboratory), and
have disease that is metastatic (stage IV [TxNxM1]) or locally advanced and not
amenable to potentially curative surgical resection (eg, clinical stage IIIB-C) Phase
II: Patients must have histologically confirmed breast cancer (MBC) that is ER
positive and/or PR positive, and HER2/neu negative (as determined by local pathology
or reference laboratory), and have disease that is metastatic (stage IV [TxNxM1]) or
locally advanced and not amenable to potentially curative surgical resection (eg,
clinical stage IIIB-C)

- HER2/neu negative disease (performed on primary tumor and/or metastatic lesion using
commercially available/approved assay in local institutional or reference
laboratory), according to American Society of Clinical Oncology (ASCO)/College of
American Pathologists (CAP) guidelines

- ER/PR expression (by standard immunohistochemical assay) on primary tumor and/or
metastatic lesion known, and classified as ER and/or PR-positive according to
ASCO/CAP guidelines (including 1-9%expression)

- National Comprehensive Cancer Network (NCCN) guidelines recommend for metastatic
breast cancer "…biopsy documentation of first recurrence, if possible, and
determination of hormone receptor status (ER and PR) and HER2 status…."; therefore,
histologic and/or cytologic confirmation of metastatic disease is encouraged whenever
feasible, but not required; in some circumstances, histologic confirmation may not be
feasible (eg, bone metastases not amenable to biopsy and elevated CA27-29 tumor
marker); for patients who have had histologic confirmation of metastatic disease, it
is required that the biopsy confirm that the metastatic tumor is ER and/or PR
positive, and HER2/neu negative; for patients in whom biopsy confirmation of
metastatic disease is not feasible, it is required that the primary tumor be ER
and/or PR-positive and HER2/neu negative

- Measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) or
non-measurable disease, with measurement obtained within 4 weeks of registration

- Phase I: Patients must have received at least one prior chemotherapy regimen for
metastatic disease Phase II: Patients must have received two or more prior
chemotherapy regimens for metastatic disease, which must have included an antitubulin
agent (eg, paclitaxel, docetaxel, vinorelbine, ixabepilone) and capecitabine; there
should be at least a 4 week interval between the last chemotherapy dose and
registration (one week for capecitabine, 2 weeks for weekly paclitaxel in the
presence of disease progression), and the patient should have recovered from acute
toxicity related to prior therapy; no prior treatment with veliparib or other PARP
inhibitors (eg, BSI 201)

- Patients must have had progressive disease after at least one line of endocrine
therapy for metastatic disease (includes relapse while receiving endocrine therapy);
there should be at least 1 week interval between the last endocrine treatment for an
aromatase inhibitor and at least 2 weeks for tamoxifen or fulvestrant

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Karnofsky >=
60%)

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Hemoglobin > 9g/dl (per manufacturer recommendation)

- Total bilirubin within normal institutional limits (unless isolated indirect
hyperbilirubinemia due to Gilbert's disease)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 × institutional upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- Patients with a history of brain metastases are eligible if they have been treated
with radiation and have stable brain metastases at least 3 months after radiation and
must also be off steroids

- Patients must be able to swallow whole capsules and tolerate oral medications

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation; being not of childbearing potential is
defined as: (1) prior hysterectomy, or (2) no menstrual period for at least 24 months

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have radiotherapy within 3 weeks prior to entering the study or those
who have not recovered from adverse events due to systemic agents administered more
than 3 weeks earlier

- Patients may not be receiving any other investigational agents

- Patients with known brain metastases with active symptoms or requiring anticonvulsive
medications, or steroids should be excluded from this clinical trial

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to veliparib (ABT-888) or cyclophosphamide used in the study

- Evidence of complete or partial bowel obstruction or other unable to take oral
medications

- Patients with malabsorption syndrome or other condition that would interfere with
intestinal absorption

- Patients unable to swallow whole capsules

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant (positive pregnancy test) or lactating women will be excluded from the
study; also, unwillingness to use effective means of contraception in subjects with
child-bearing potential will be excluded from the study; women of child-bearing
potential must use two forms of contraception (i.e., barrier contraception and one
other method of contraception) at least 4 weeks prior to study entry, for the
duration of study participation

- Patients with active severe infection; known infection with human immunodeficiency
virus (HIV), hepatitis B virus, hepatitis C virus, or severe concurrent illness will
be excluded from the study; HIV-positive patients on combination antiretroviral
therapy are ineligible

- Patients with a history of seizure disorder requiring antiepileptics who have had a
seizure episode within the last 6 months

- Prior treatment with veliparib (ABT-888) or other PARP inhibitors (e.g., olaparib)