Veliparib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer or Metastatic Breast Cancer

PRIMARY OBJECTIVES:

I. To determine the recommended Phase II dose of ABT-888 (veliparib) given in combination
with pegylated liposomal doxorubicin (pegylated liposomal doxorubicin hydrochloride) (PLD -
40 mg/m2 every 4 weeks) in patients with ovarian or breast cancer.

SECONDARY OBJECTIVES:

I. To determine the toxicity profile of the ABT-888 plus PLD combination. II. To determine
the effects of ABT-888 on the pharmacokinetics of PLD. III. To determine the efficacy of
ABT-888 plus PLD in ovarian and breast cancer.

OUTLINE: This is a dose-escalation study of veliparib.

Patients receive veliparib orally (PO) twice daily (BID) on days 1-14 and pegylated liposomal
doxorubicin hydrochloride intravenously (IV) over 60 minutes on day 1. Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 1 year and
then every 6 months for 2 years.

Inclusion Criteria:

- Histologically confirmed diagnosis of recurrent or residual epithelial ovarian cancer,
primary peritoneal carcinoma or fallopian tube carcinoma, OR histologically confirmed
metastatic breast cancer, that is estrogen receptor (ER)-negative, progesterone
receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)/neu
negative (as determined by local pathology laboratory)

- Prior chemotherapy:

- Ovarian cancer: patients with no prior PLD exposure are eligible after failure of
platinum-containing chemotherapy; no more than 2 prior platinum containing
regimens is permitted; dose escalating cohorts only: patients already on PLD are
also eligible if they are receiving PLD beyond 3 cycles without prohibitive (i.e.
no grade 3 or 4) skin or mucosal toxicities, and showing no progressive disease
compared to a computed tomography (CT) scan obtained 2 or more months earlier;
these patients are eligible in spite of any progression from baseline determined
prematurely (i.e., applicable to those patients who are deemed in their best
interest to continue to receive PLD after a CT obtained at 2 or 3 months has
shown progression from baseline)

- Breast cancer: patients may have received 0-2 prior chemotherapy regimens
for metastatic disease; breast cancer patients may not have received prior
PLD, and will not be eligible for the expanded cohort A

- Interval between prior chemotherapy and registration for breast and ovarian
cancer; there should be at least a 3 week interval between the last
chemotherapy regimen and registration, and the patient should have recovered
from acute toxicity related to prior therapy (6 weeks if the last regiment
included BCNU or mitomycin C)

- Dose escalating cohorts only: patients will be categorized in the following
strata based upon prior PLD exposure: Stratum A -patients with ovarian
cancer who have had prior PLD exposure and received at least 3 cycles of PLD
without prohibitive (i.e. no grade 3 or 4 skin toxicity) and have not had
progressive disease; Stratum B: patients with ovarian or breast cancer who
have had no prior PLD exposure

- Eastern Cooperative Oncology Group (ECOG) performance score 0-2

- All potential subjects should be evaluated for whether breast cancer (BRCA)1-2 testing
is medically appropriate; individuals who have a 10% or higher risk of having a
BRCA1-2 mutation (Myriad tables at www.myriad.com) are encouraged (but not required)
to have mutation testing and results known; information regarding mutation status
(positive [including specific mutation], negative, or unknown) and projected risk of
having a mutation (as determined by Myriad tables) will be collected at the time of
diagnosis

- Non-measurable and/or measurable disease by Response Evaluation Criteria in Solid
Tumors (RECIST) criteria, or abnormal cancer antigen (CA)-125 to levels (in patients
with ovarian cancer) at least 1.5 x normal documented by two independent measurements
at least 4 weeks apart

- Ability to give voluntary informed consent and to comply with treatment and required
tests

- Ability to tolerate oral medications

- Female subjects age >= 18 years (males with breast cancer are eligible)

- Absolute neutrophil count >= 1500/mL

- Platelets >= 100,000/mL

- Creatinine =< 1.5 mg/dL

- Total bilirubin =< 1.5 x institutional upper limit of normal

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x
institutional upper limit of normal (=< 5 x institutional upper limit of normal if
evidence of liver metastasis)

- Left ventricular ejection fraction at or above institutional lower limit of normal
(obtained within 8 weeks of registration by multigated acquisition [MUGA] scan or
echocardiogram; the same test performed at baseline should be repeated after every 3
cycles of therapy)

- 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; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately

Exclusion Criteria:

- Known central nervous system (CNS) metastases with active symptoms, or requiring
anticonvulsive medications, or steroids

- Prior chemotherapy (except PLD in Dose Escalation Cohorts only) or any investigational
agent within 3 weeks prior to registration

- Prior radiation therapy to whole pelvis or greater amount of marrow-forming bone

- Prior or current non-gynecologic or non-breast malignancy within 5 years except
non-melanoma skin cancer

- Patients with active severe infection; known infection with human immunodeficiency
virus (HIV), hepatitis B virus, hepatitis C virus, or severe concurrent illness

- Patients with any non-malignant intercurrent illness (e.g. cardiovascular, pulmonary,
central nervous system disease) which is either poorly controlled with currently
available treatment, or which is of such severity that the investigators deem it
unwise to enter the patient on protocol

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

- Pregnant (positive pregnancy test) or lactating; unwillingness to use effective means
of contraception in subjects with child-bearing potential

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