This phase I trial studies the side effects and best dose of veliparib when given with or
without mitomycin C in treating patients with solid tumors that have spread to other places
in the body, cannot be removed by surgery or have come back. Veliparib may stop the growth
of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in
chemotherapy, such as mitomycin C, work in different ways to stop the growth of tumor cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving veliparib together with mitomycin C may kill more tumor cells.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Inclusion Criteria:
- Patients must have a histologically confirmed solid malignancy that is metastatic, or
unresectable, or recurrent, for which no curative or standard of care exist, or this
standard of care is no longer effective
- Tumors have been shown to be deficient for the FA pathway, based on Fanconi anemia
triple stain immunofluorescence (FATSI) screening
- Up to two chemotherapy regimens for metastatic disease are allowed; in addition,
prior adjuvant/neo-adjuvant chemotherapy, hormonal therapy, molecular targeted
therapy or estrogen receptor B (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
nitrosoureas or mitomycin C; previous use of mitomycin C would be restricted to
topical applications (bladder cancer) or chemoembolization (e. g., liver tumors)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Life expectancy of greater than 3 months
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count (ANC) >= 1,500/mcL
- Hemoglobin >= 9 g/dL
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limit
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 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
- 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 should be able to swallow capsules
- EXPANSION COHORT:
- Diagnosis of colorectal malignancy
- Absence of Fanconi anemia, complementation group D2 (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); 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; breastfeeding should be discontinued
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible
- Patients with active seizure or a history of seizures
- Patients previously treated with PARP inhibitors; with the exception of patients
enrolled on Arm 2 who may have had prior treatment with PARP inhibitors as
monotherapy