Veliparib With or Without Mitomycin C in Treating Patients With Metastatic, Unresectable, or Recurrent Solid Tumors

Inclusion Criteria:

• Histologically confirmed solid tumor malignancy for which no curative or standard therapy exists or for which standard therapy is no longer effective

  • Metastatic, unresectable, or recurrent disease
• Tumor demonstrates deficiency for the Fanconi anemia pathway, based on FATSI immunofluorescence screening

• Up to two chemotherapy regimens for metastatic disease are allowed; in addition, prior adjuvant/neo- adjuvant chemotherapy, hormonal therapy, molecular targeted therapy or Erb inhibitor treatments (e.g., erlotinib, herceptin, sorafenib, sunitinib) will be allowed and will not count towards eligibility

  • At least 4 weeks must elapse since prior chemotherapy or radiation therapy (two weeks for erlotinib, hormonal therapy, or limited field palliative radiation to bone, brain, or radiosurgery), 6 weeks if the last regimen included nitrosureas or Mitomycin C
  • Given the association of cumulative doses of Mitomycin C with toxicity, previous use of Mitomycin C would be restricted to topical applications (bladder cancer) or chemoembolization (e.g., liver tumors)
• Eastern Cooperation Oncology Group (ECOG) performance status (PS) =< 2 OR Karnofsky >= 60%
• Life expectancy > 3 months
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Hemoglobin >= 9 g/dL
• Platelet count >= 100,000/mcL
• Total bilirubin within normal institutional limit
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limit OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• The effects of ABT-888 on the developing human fetus are unknown, and Mitomycin C could be harmful to the fetus; for this reason, 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
• Fertile patients must use effective contraception
• Able to swallow capsules

• Ten additional evaluable patients will be accrued to the Arm 2 (MMC + ABT-888) therapeutic portion of the study, once the MTD and recommended phase 2 of the study has been defined; eligibility for these patients includes the following:

  • Diagnosis of colorectal malignancy
  • Absence of FANCD2 foci by FATSI screening
  • Presence of biopsiable lesion by imaging
  • Consent to a baseline (prior to treatment) tumor biopsy and for a repeat biopsy at the time of progression on the event that an antitumor response is demonstrated on the MMC-ABT-888 regimen
  • Same eligibility as above, except that they will have no limitations related prior number of chemotherapy regimens given; patients could have received prior treatment with PARP inhibitors if used as single agent

Exclusion Criteria:

• Patients may not be receiving any other investigational agents
• Patients with known central nervous system (CNS) metastases (unless previously resected or irradiated and not clinically active) should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; patients with CNS metastases must be stable after therapy for > 3 months and off steroid treatment prior to study enrollment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition as ABT-888 or Mitomycin C
• 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 because ABT-888 and Mitomycin C are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ABT-888 and Mitomycin, breastfeeding should be discontinued
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions or increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• Patients with active seizure or a history of seizures
• Patients previously treated with poly ADP-ribose polymerase (PARP) inhibitors; with the exception of patients enrolled on Arm 2 who may have had prior treatment with PARP inhibitors as monotherapy