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

This is an interventional treatment trial for Adenocarcinoma of the Pancreas Read More

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