Phase I Study of ABT-888, PARP Inhibitor, and Pegylated Liposomal Doxorubicin (PLD) in Recurrent Gynecologic Cancer and Breast Cancer

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 ER-negative, PR-negative, and HER2/neu
negative (as determined by local pathology laboratory)

- Histological confirmation may be from original pathology. Patient does not
require new biopsy for recurrent, residual or metastatic disease that is
clinically diagnosed

- Prior chemotherapy:

- Ovarian cancer: (a) Patients with no prior PLD exposure are eligible after
failure of platinum-containing chemotherapy; no more than 2 prior platinum
containing regimens is permitted; (b) 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 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)

- Patients will be categorized in the following strata based upon prior PLD
exposure: (A) 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; (B)
Stratum B: Patients with ovarian or breast cancer who have had no prior PLD
exposure

- ECOG performance score 0-2

- All potential subjects should be evaluated for whether BRCA1-2 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 RECIST criteria, or abnormal CA-125 to
levels (in patients with ovarian cancer) at least 1.5x 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 =< 1.5mg/dL

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

- AST and ALT =< 3x institutional upper limit of normal (=< 5x 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 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 CNS metastases with active symptoms, or requiring anticonvulsive medications,
or steroids

- Prior chemotherapy (except PLD) 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 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