Veliparib in Combination With Carboplatin and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors

Inclusion Criteria:

• Histologically or cytologically confirmed solid tumor that has evidence of metastatic spread (stage IV) or is locally advanced and unresectable

  • Patients with breast cancer may have estrogen receptor positive or negative (ER+ or ER-) disease
  • Patients with breast cancer may not be HER2-positive ( 3+), or fluorescent in situ hybridization (FISH) ratio > 2.2

  • Patients in the biopsy expansion cohort must have "triple negative" breast cancer defined as:

    • Estrogen receptor staining < 10%; progesterone receptor staining <10%; Her 2 < 2.2 by FISH, or immunohistochemistry (IHC) 0-2+

• Patients enrolled in the expanded cohort with mandatory biopsies must:

  • Have accessible tumors
  • Not be on therapeutic anticoagulation
  • Have signed informed consent form

• Patients may have been previously treated

  • In the dose escalation cohort, there is no limit to prior therapies
  • In the expansion cohort, patients may have only had 1-3 prior regimens for metastatic disease

  • Patients may have received prior carboplatin, paclitaxel, or poly (ADP-ribose) polymerase (PARP) inhibitor therapy as part of their previous treatment regimens

    • However, patients may NOT have received prior therapy with paclitaxel, carboplatin, and PARP inhibitor in combination
• Patients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for > 3 months and must be off steroid treatment prior to study enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 (Karnofsky PS 60-100%)
• Life expectancy > 2 months
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Total bilirubin =< 1.5 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 times ULN
• Creatinine normal OR creatinine clearance >= 60 mL/min
• Able to swallow pills
• Not pregnant or nursing
• Negative pregnancy test
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) prior to study entry and for the duration of study participation
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in study
• No 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
• No active seizure or history of seizure disorder
• No peripheral neuropathy of severity greater than grade 1
• More than 4 weeks since prior chemotherapy (6 weeks for carmustine [BCNU], nitrosoureas, or mitomycin C) and recovered
• More than 2 weeks since prior radiotherapy
• Concurrent treatment with bisphosphonates, or other bone anti-resorptive agent such as denosumab is allowed; concurrent treatment with hormonal therapy (tamoxifen, ovarian suppression with gonadotropin-releasing hormone [GNRH] agonists, aromatase inhibitors) or trastuzumab therapy is NOT allowed in breast cancer patients; prostate cancer patients may continue GNRH agents
• No other concurrent investigational agents