A PHASE II EVALUATION OF THE POLY (ADP-RIBOSE) POLYMERASE (PARP) -1 AND -2 INHIBITOR VELIPARIB (ABT-888) (IND #77840) (NSC #737664) IN THE TREATMENT OF PERSISTENT OR RECURRENT EPITHELIAL OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER PATIENTS WHO CARRY A GERMLINE BRCA1 OR BRCA2 MUTATION

Inclusion Criteria:

- Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or
primary peritoneal carcinoma AND carry a germline mutation in BRCA1 or BRCA2
(confirmation required via Myriad test report); histologic documentation of the
original primary tumor is required via the pathology report

- All patients must have measurable disease as defined by Response Evaluation Criteria
in Solid Tumors(RECIST); measurable disease is defined as at least one lesion that
can be accurately measured in at least one dimension (longest diameter to be
recorded); each lesion must be ≥ 10 mm when measured by computed tomography (CT),
magnetic resonance imaging (MRI), or caliper measurement by clinical exam; or ≥ 20 mm
when measured by chest x-ray; lymph nodes must be ≥ 15 mm in short axis when measured
by CT or MRI

- Patient must have at least one "target lesion" to be used to assess response on this
protocol as defined by RECIST; tumors within a previously irradiated field will be
designated as "non-target" lesions unless progression is documented or a biopsy is
obtained to confirm persistence at least 90 days following completion of radiation
therapy

- Patients must have had one prior platinum-based chemotherapeutic regimen for
management of primary disease containing carboplatin, cisplatin, or another
organoplatinum compound; this initial treatment may have included intraperitoneal
therapy, consolidation, biologic/targeted (non-cytotoxic) agents, or extended therapy
administered after surgical or non-surgical assessment

- Patients with both platinum-sensitive and platinum-resistant disease are eligible

- Platinum-sensitive ovarian cancer is defined as patients who respond to
platinum-based therapy (complete [CR]or partial response [PR]) and then
progress/recur more than 6 months after their last platinum dose (i.e.,
platinum-free interval is > 6 months)

- Platinum-resistant ovarian cancer is defined as patients who respond to
platinum-based therapy (CR or PR) and then progress/recur within 6 months of
their last platinum dose (i.e., platinum-free interval is ≤ 6 months)

- No patients with platinum-refractory disease

- Platinum-refractory ovarian cancer is defined as patients who have
progression of disease while receiving platinum-based chemotherapy or who
fail to achieve at least a PR to platinum-based chemotherapy (i.e., best
response to platinum-based chemotherapy is stable disease)

- No patients with history or evidence upon physical examination of central nervous
system (CNS) disease, including primary brain tumor, seizures not controlled with
standard medical therapy, or any brain metastases

- Patients who have received one prior cytotoxic regimen must have a Gynecologic
Oncology Group (GOG) Performance Status of 0, 1, or 2; patients who have received two
or three prior regimens must have a GOG Performance Status of 0 or 1

- Patients should be free of active infection requiring antibiotics (with the exception
of uncomplicated urinaty tract infection [UTI])

- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

- Platelets greater than or equal to 100,000/mcl

- Creatinine less than or equal to 1.5 times institutional upper limit of normal (ULN)

- Bilirubin less than or equal to 1.5 times ULN

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or
equal to 3 times ULN

- Alkaline phosphatase less than or equal to 2.5 times ULN

- Patients must have signed an approved informed consent and authorization permitting
release of personal health information

- Patients of childbearing potential must have a negative pregnancy test prior to the
study entry and be practicing an effective form of contraception

- Patients with a history of other invasive malignancies, with the exception of
non-melanoma skin cancer and other specific malignancies, are excluded if there is
any evidence of other malignancy being present within the last three years

- No ability or unwillingness to swallow pills

- No patients with clinical symptoms or signs of gastrointestinal obstruction and/or
who require parenteral hydration or nutrition

- No patients who are pregnant or nursing

- Patients with seizures or history or seizures are ineligible

- Patients with history or evidence upon physical examination of CNS disease, including
primary brain tumor, any CNS metastases, or history of cerebrovascular accident (CVA,
stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months
of the first date of treatment on this study are ineligible; patients with CNS
metastases must be stable for > 3 months after treatment and off steroid treatment
prior to study enrollment

- See Disease Characteristics

- Recovered from effects of recent surgery, radiotherapy, or chemotherapy

- Any hormonal therapy directed at the malignant tumor must be discontinued at least
one week prior to registration; continuation of hormone replacement therapy is
permitted

- Any other prior therapy directed at the malignant tumor, including chemotherapy,
biologic/targeted (non-cytotoxic) agents, and immunologic agents, must be
discontinued at least three weeks prior to registration; patients receiving
nitrosoureas or mitomycin C must discontinue 6 weeks prior to the initiation of study
treatment

- Any prior radiation therapy must be discontinued at least four weeks prior to
registration

- Patients are allowed to receive, but are not required to receive, two additional
cytotoxic regimens for management of recurrent or persistent disease

- Patients are allowed to receive, but are not required to receive, biologic/targeted
(non-cytotoxic) therapy for management of recurrent or persistent disease

- Patients are allowed to receive, but are not required to receive, biologic/targeted
(non-cytotoxic) therapy as part of their primary treatment regimen

- No patients who have had previous treatment with veliparib (ABT-888) or any other
poly (ADP-ribose) polymerase (PARP) inhibitor (including olaparib)

- Iniparib (BSI-201) cannot inhibit PARP1 at pharmacologically achievable
concentrations, therefore prior iniparib therapy is allowed

- Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis OTHER THAN for the treatment of ovarian, fallopian tube, or primary
peritoneal cancer within the last three years are excluded; prior radiation for
localized cancer of the breast, head and neck, or skin is permitted, provided that it
was completed more than three years prior to registration, and the patient remains
free of recurrent or metastatic disease

- Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER
THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer
within the last three years are excluded; patients may have received prior adjuvant
chemotherapy for localized breast cancer, provided that it was completed more than
three years prior to registration, and that the patient remains free of recurrent or
metastatic disease