Veliparib and Floxuridine in Treating Patients With Metastatic Epithelial Ovarian, Primary Peritoneal Cavity, or Fallopian Tube Cancer

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of the combination of ABT-888 (veliparib) and
intraperitoneal (IP) floxuridine in adult patients with advanced ovarian, primary peritoneal
or fallopian tube cancer.

SECONDARY OBJECTIVES:

I. To describe the adverse event profile associated with this treatment combination.

II. To assess for preliminary evidence of efficacy, such as tumor responses, of the treatment
combination.

III. To assess progression free survival (PFS) in the maximum tolerated dose (MTD) cohort.

TERTIARY OBJECTIVES:

I. Assess the pharmacokinetic profile of ABT-888 and floxuridine when given in combination.

II. Assess whether the presence of mutations in the homologous recombination pathway or loss
of expression of non-homologous end joining (NHEJ) components correlates with response to
floxuridine + ABT-888.

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

Patients receive veliparib orally (PO) twice daily (BID) on days 1-10 and floxuridine IP on
days 3-5. Courses repeat every 21 days in the absence of disease progression or unacceptable
toxicity.

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

Inclusion Criteria:

- Histologically confirmed epithelial ovarian, primary peritoneal or fallopian tube
malignancy that is metastatic and for which standard curative measures do not exist

- Disease confined to the intraperitoneal and retroperitoneal cavity; Note: nodal
disease below the diaphragm, implants adherent to the surface of the liver or
intrahepatic lesions will not be exclusionary; patients remain eligible if all
intrahepatic tumor is debulked or ablated by the time treatment is initiated

- EXPANSION PHASE ONLY: Evaluable or measurable disease with the largest nodule
measuring less than 5 cm in greatest dimension by radiographic imaging after debulking
procedure

- Candidate for and willingness to have a surgically placed intraperitoneal catheter and
tissue acquisition at the time of port placement; note: if an intraperitoneal catheter
is already in place, a tumor biopsy will still be required; a guided core-needle
biopsy is sufficient in these cases

- Able to swallow and absorb the medication

- Obtained =< 7 days prior to registration: Absolute neutrophil count (ANC) >= 1500/mm^3

- Obtained =< 7 days prior to registration: Platelets (PLT) >= 100,000/mm^3

- Obtained =< 7 days prior to registration: Total bilirubin =< 1.5 x institutional upper
limit of normal (ULN)

- Obtained =< 7 days prior to registration: Creatinine =< 1.5 x institutional ULN

- Obtained =< 7 days prior to registration: Aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) =< 3 x institutional ULN

- Obtained =< 7 days prior to registration: Hemoglobin (Hgb) > 9.0 mg/dl

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

- Ability to provide informed written consent

- Life expectancy >= 12 weeks

- Women of childbearing potential only: negative pregnancy test done =< 7 days prior to
registration

Exclusion Criteria:

- Known standard therapy for the patient's disease that is potentially curative or
definitely capable of extending life expectancy; note: patients with recurrent
platinum-sensitive ovarian, primary peritoneal or fallopian tube will be allowed, if
the investigator believes the study treatment is a better alternative to initiation
platinum-based chemotherapy, such as patients with a prior platinum allergy or low
volume disease for whom platinum-based therapy is deferred until a later date

- More than 4 prior chemotherapy regimens; note: repeat use of regimens count as 1 prior
regimen; switching front-line therapy regimens (for example, from intraperitoneal to
intravenous therapy) for reasons other than progression will count as 1 prior therapy;
bevacizumab and other 'targeted' agents will count in the total number of prior
regimens; vaccine therapies will not count in the total of prior therapies

- 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

- Any of the following prior therapies:

- Chemotherapy =< 28 days prior to registration

- Mitomycin C/nitrosoureas =< 42 days prior to registration

- Immunotherapy =< 28 days prior to registration

- Biologic therapy =< 28 days prior to registration

- Radiation therapy =< 28 days prior to registration

- Investigational therapy or any ancillary therapy considered investigational
(utilized for a non-Food and Drug Administration [FDA] approved indication and in
the context of a research investigation) =< 28 days prior to registration

- Prior poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor
therapy

- Failure to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment

- Significant cardiovascular disease defined as congestive heart failure (New York Heart
Association class III or IV cardiac disease), angina pectoris requiring nitrate
therapy or recent myocardial infarction (=< 6 months prior to registration)

- Metastatic disease outside the intraperitoneal cavity and retroperitoneum,
intrahepatic lesions, or pleural effusions; significant ascites precluding catheter
placement; exception: intrahepatic lesions removed or planning to be removed during
the debulking procedure

- Any of the following:

- Nursing women

- Pregnant women

- Women of childbearing potential who are unwilling to employ adequate
contraception (non-barrier method)

- Immunocompromised patients (other than that related to the use of corticosteroids)
with the exception of patients known to be human immunodeficiency virus (HIV) positive
and have a cluster of differentiation 4 (CD4) count > 400 and do not require
antiretroviral therapy

- Receiving any other investigational agent that would be considered a treatment for the
primary neoplasm

- Other active malignancy =< 1 year prior to registration

- EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix

- NOTE: If there is a history or prior malignancy, they must not be receiving other
specific treatment for their cancer