Veliparib, Oxaliplatin, and Capecitabine in Treating Patients With Advanced Solid Tumors

Inclusion Criteria:

Histologically or cytologically confirmed solid tumors that fulfill ≥ 1 of the following criteria:

BRCA1/2 mutation and a BRCA-related malignancy

Patients without a known BRCA mutation must have a probability of harboring a BRCA gene mutation as assessed by BRCAPRO computer program
Patients with a probability of having genetic mutation ≥ 20% or a BRCA mutation based on a non-Myriad test, must have a formal BRCA testing by Myriad Genetic Laboratories
Patients with known deleterious BRCA 1 or 2 mutation or a mutation of uncertain significance
Patients who refuse BRCA testing not allowed unless they have another acceptable histology
First- or second-line metastatic colorectal cancer
Any-line metastatic mucinous ovarian cancer
Any line of other metastatic gastrointestinal malignancies in which oxaliplatin has shown some activity (i.e., gastric or pancreatic adenocarcinoma)
Patients with uncontrolled CNS metastasis are not eligible; patients with CNS metastases who have had them treated and are stable for > 3 months will be eligible; patients must be off steroid treatment prior to study enrollment

Measurable disease

Patients with ovarian cancer who have a pre-treatment CA 125 level of at least twice the upper limit of normal allowed
ECOG performance status (PS) 0-2 (Karnofsky 60-100%)
Life expectancy > 3 months
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver metastases)
Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
Fertile patients must use adequate contraception (i.e., hormonal, barrier method of birth control, or abstinence)
Not pregnant or nursing
Negative pregnancy test
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, any of the following:

Ongoing or active infection
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
Psychiatric illness and/or social situations that would limit compliance with study requirements
No history of positive serology for hepatitis A, B, or C, liver disease, or other forms of hepatitis or cirrhosis
Patients who have active seizures or history of seizures are ineligible

No condition that impairs the ability to swallow and retain veliparib capsules, including any of the following:

Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
Prior surgical procedures affecting absorption
Active peptic ulcer disease
No malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction
No peripheral neuropathy ≥ grade 2
No prolonged QTC > 450 msec (male) or QTC > 470 (female)
No concurrent combination antiretroviral therapy for HIV-positive patients

Recovered from adverse events of prior therapy or prior surgical procedures

Patients with chronic grade 1 or 2 adverse events that are not expected to improve are allowed at investigator's discretion
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
At least 4 weeks since prior radiotherapy with no > 35% of marrow irradiation
Prior fluoropyrimidine allowed
Prior veliparib allowed provided it was part of a single- or limited-dosing study, such as a phase 0 study
Prior capecitabine allowed provided patient tolerated 3500 mg/m² for 7 days out of 14 days
No other prior investigational agents
No prior oxaliplatin