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 human epidermal growth receptor -2 (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 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 must not have received chemotherapy within 4 weeks of starting study (or 6 weeks if prior treatment was with carmustine [BCNU] or mitomycin C)
  • Patients must not have received radiation within 2 weeks of starting study
• Eastern Cooperative Oncology Group (ECOG) performance status (PS)< 2 (Karnofsky > 60%)
• Life expectancy > 2 months
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelet count >= 100,000/mcL
• Total bilirubin =< 1.5 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times ULN
• Creatinine normal within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels above institutional normal
• Must able to swallow pills

• Pregnant women are excluded from this study

  • 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

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

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

Exclusion Criteria:

• Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 2 weeks (4 weeks for central nervous system [CNS] metastases) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in study
• 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
• 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 veliparib
• Active seizure or history of seizure disorder
• Patients with 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
• Patients who undergo biopsy as part of the study in the expanded dose cohort should not be on anti-coagulants or have a pre-existing coagulopathy
• Peripheral neuropathy of severity greater than grade 1