A Study of ABT-888 in Combination With Carboplatin and Gemcitabine in Subjects With Advanced Solid Tumors

• Pharmacokinetics Area Under the Curve (AUC) [ Time Frame: Timepoints: 30 and 45 minutes, 1,1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5,6,6.5, 7 and 8 hours past dose ] [ Designated as safety issue: No ]
• Safety assessment: Electrocardiogram [ Time Frame: Screening, Day 8 of each Cycle of drug and Final Visit ] [ Designated as safety issue: Yes ]
• Safety assessment: Clinical Laboratory Tests [ Time Frame: Screening, Day 1 and Day 8 of each cycle, Final Visit and 30 Day Follow-up Visit ] [ Designated as safety issue: Yes ]
  Hematology and Chemistry
• Physical exam including vital signs [ Time Frame: Screening, Cycle 1 Day 8, Day 1 of all cycles starting with Cycle2, Final Visit and 30 Day Follow-up Visit ] [ Designated as safety issue: Yes ]
  Physical exam including blood pressure, pulse and temperature
• Safety assessment: Adverse event assessments [ Time Frame: All study visits ] [ Designated as safety issue: Yes ]
  Collect all adverse events at each visit
• Tumor assessment [ Time Frame: Screening, every nine weeks and Final Visit ] [ Designated as safety issue: No ]
  Computerized tomography (CT) scan of chest, abdomen and pelvis to assess tumor burden

• Pharmacokinetics of ABT-888 when given in combination with carboplatin and gemcitabine [ Time Frame: Cycle 1 through Cycle 4 ] [ Designated as safety issue: No ]
• Safety assessments (i.e. ECG, clinical laboratory tests, vital signs, adverse events assessments, physical exams, CT scans) [ Time Frame: Screening through final visit ] [ Designated as safety issue: Yes ]

The purpose of this study is to determine the maximum tolerated dose and establish the recommended Phase 2 dose of ABT-888 when administered in combination with carboplatin and gemcitabine in subjects with advanced solid tumors.

• Drug: veliparib (ABT-888)
  Dosing orally twice daily starting Cycle 2 Day 1- through 21 adjusted for subsequent cohorts using a continuous reassessment method.
• Drug: carboplatin
  Carboplatin will be dosed on Day 1 of each cycle, intravenously.
• Drug: gemcitabine
  Dosing on Days 1 and 8 of each Cycle, intravenously.
  Other Name: Gemzar

Inclusion Criteria:

• Subject must be 18 years of age.
• Histologically or cytologically confirmed solid tumors that are metastatic or unrespectable for which carboplatin/gemcitabine is a treatment option.
• Eastern Cooperative Group performance score of 0 to 2.
• Adequate hematologic, hepatic and renal function
• Subject has received up to 2 DNA damaging or cytotoxic regimens in the past five years

Exclusion Criteria:

• Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy within 28 days prior to study administration.
• Subjects with known history of brain metastases and primary CNS tumors.
• Hypersensitivity reactions to platinum compounds or gemcitabine.
• Clinically significant and uncontrolled major medical conditions
• Active malignancy within the past 5 years except for any cancer in situ cured or non-melanoma carcinoma of the skin.