Veliparib in Treating Patients With Malignant Solid Tumors That Did Not Respond to Previous Therapy

Inclusion Criteria:

• Histologically or cytologically confirmed malignant solid tumor meeting ≥ 1 of the following criteria:

  • Documented BRCA1/2 mutation AND a BRCA-related malignancy (e.g., primarily breast or ovarian cancer, but may include prostate or pancreatic cancer)

  • Platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer

    • Platinum-refractory is defined as progression or recurrence within 6 months of initial platinum response
    • No platinum-resistant disease, defined as no prior response to platinum-based therapy (i.e., evidence of progression within 2-3 courses of beginning initial platinum-based therapy)
    • Patients with platinum-sensitive disease must have known BRCA mutations

  • Basal-like breast cancer, defined as estrogen and progesterone receptor-negative, HER2-negative, and/or expression profile of EGFR and cytokeratins 5/6 consistent with basal phenotype

    • "Triple-negative" phenotype (i.e., negative hormone and HER2 receptors) allowed

      • Patients with known "triple-negative" phenotype but unknown basal phenotype will have their tumor blocks assessed for basal markers
• Progressive disease after standard therapy OR no acceptable standard treatment options available

• Patients without a known BRCA mutation must have archived tumor tissue samples available for assessment of BRCA1/2 protein expression by immunohistochemistry

  • Patients without a known, documented BRCA mutation from Myriad Genetic Laboratories must have a probability of harboring a BRCA gene mutation as assessed by BRCAPRO computer program

    • Patients with a probability of harboring a BRCA gene mutation of ≥ 20% must undergo formal BRCA testing by Myriad Genetic Laboratories
    • Patients with a diagnosis of a BRCA mutation based on a non-Myriad test must undergo Myriad BRCA gene sequencing
  • Known deleterious BRCA1 or 2 mutation or a mutation of uncertain significance allowed

• Patients enrolled on dose levels VI-IX must be willing to undergo skin biopsies and hair sample collection before starting treatment and on day 4

  • Patients who are receiving therapeutic doses of anticoagulation are exempt

• Patients with BRCA mutations who are enrolled in the 6-patient expansion group at the MTD (or dose level IX) must agree to tumor biopsies

  • Tumors must be easily accessible for biopsies with low likelihood of complication
  • Patients should not be on therapeutic doses of anticoagulation
• Patients with BRCA mutations who are enrolled in the 6-12 patient expansion group at the MTD (or dose level IX) must agree to tumor biopsies; therefore patients enrolled in this cohort should have tumors easily accessible for biopsies with low likelihood of complication and these patients should not be on therapeutic doses of anticoagulation
• Hormone receptor status not specified
• Menopausal status not specified
• ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
• Life expectancy > 3 months
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 2.0 mg/dL
• Transaminases ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance > 50 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV infection allowed provided CD4 count > 500/mm³
• Able to swallow pills

• No concurrent uncontrolled illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit compliance with study requirements
• No concurrent protease inhibitors for patients with HIV infection
• Recovered from all prior therapy
• More than 4 weeks since prior major surgery, radiotherapy, or chemotherapy (6 weeks for nitrosoureas or mitomycin C)

• At least 4 weeks since prior flutamide (6 weeks for bicalutamide) for prostate cancer

  • Concurrent ongoing luteinizing hormone-releasing hormone agonist therapy for prostate cancer required
• Concurrent IV bisphosphonates for bone metastases or hypercalcemia allowed provided treatment was initiated prior to study entry
• No concurrent chemotherapy
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• 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 and must have a life expectancy secondary to that of 3 months or greater to be eligible
• Active seizure or history of seizure disorder are excluded