Veliparib, Paclitaxel, and Carboplatin in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery and Liver or Kidney Dysfunction

PRIMARY OBJECTIVES:

I. To determine the pharmacokinetics and pharmacodynamics of ABT-888 (veliparib) in patients
with varying degrees of renal or hepatic dysfunction.

II. To determine the maximum tolerated dose (MTD) of ABT-888 in combination with carboplatin
and paclitaxel for patients with varying degrees of liver or kidney dysfunction.

III. To provide dosing recommendations for ABT-888 in combination with carboplatin and
paclitaxel based on degree of hepatic and renal impairment.

SECONDARY OBJECTIVES:

I. To define the dose-limiting toxicity (DLT) and other toxicities associated with the use of
this combination in patients with varying degrees of renal or hepatic dysfunction.

II. To evaluate the pharmacokinetic parameters of ABT-888, carboplatin, and paclitaxel when
administered as a combination in patients with varying degrees of renal or hepatic
dysfunction.

III. To evaluate the pharmacodynamic measurement of poly-ADP-ribosylated (PAR) and platinum
adducts in tumor cells associated with the use of this combination in patients with varying
degrees of renal or hepatic dysfunction.

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

Patients receive veliparib* orally (PO) twice daily (BID) on days 1-7 and paclitaxel
intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 3. Treatment
repeats every 21 days for 6 courses in the absence of disease progression or unacceptable
toxicity.

NOTE: * All patients receive a single dose of veliparib PO on day -6 before course 1 (except
patients with very severe renal dysfunction who receive veliparib on day -5 or -6 to coincide
with a dialysis day).

After completion of study treatment, patients are followed up for 4 weeks.

Inclusion Criteria:

- Patients must have histologically confirmed malignancy that is radiologically
evaluable and metastatic or unresectable, for which standard curative or palliative
measures do not exist or are no longer effective, and for which there is expectation
of response to the combination of carboplatin/paclitaxel (i.e., lung, ovarian, breast,
melanoma, head and neck, endometrial, urothelial, testicular, esophageal, carcinoma of
unknown primary); for indications not listed, eligibility based on disease must be
verified by the principal investigator before they are considered

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Life expectancy of greater than 12 weeks

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Hemoglobin >= 8.0 g/dL

- Patients with all degrees of renal dysfunction are allowed including patients on
hemodialysis; patients with mild to severe hepatic dysfunction are allowed as defined
below:

- Total bilirubin =< 5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 10 x ULN

- For patients with a recently placed biliary stent, patients should have consistent
results within a hepatic group from two laboratory readings within 3 days apart, taken
at least 10 days following biliary stent placement; for patients with a biliary stent
placed over 2 months ago, no obstruction or blockage can have occurred within the last
2 months

- 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

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

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those whose adverse event
due to agents administered more than 4 weeks earlier have not resolved or stabilized;
patients who have been administered ABT-888 as part of a single or combination, phase
0 or I study, should not necessarily be excluded from participating in this study
solely because of receiving prior ABT-888

- Patients may not be receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ABT-888 or other agents used in study

- Peripheral neuropathy of severity greater than grade 1

- Inability to take oral medications on a continuous basis

- Evidence of bleeding diathesis

- Patients with central nervous system (CNS) metastases must be stable after therapy for
CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for at
least 3 months and must be off steroid treatment prior to study enrollment

- 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 women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with ABT-888; these potential risks may also apply to other
agents used in this study

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible; however, HIV-positive patients without an acquired immune
deficiency syndrome (AIDS)-defining diagnosis who are not receiving agents with the
potential for pharmacokinetic (PK) interactions with ABT-888 may be eligible

- Patients with both hepatic and renal dysfunction will also be excluded

- Patients who received and progressed on the combination of carboplatin/paclitaxel will
not be eligible

- Active seizure or history of seizure disorder