Irinotecan and ABT-888 in Treating Patients With Metastatic or Unresectable Cancer

Inclusion Criteria:

• Bilirubin =< 1.5 times ULN
• Patients must have tumors determined to be easily accessible for biopsy (e.g. pleural-based lesions, peripheral lymph nodes, soft tissue metastases, or large liver metastases)
• Archival tissue block or paraffin sample from archival tissue block (approximately 10 sections) for use in pharmacodynamic correlative studies must be available

• No known active brain metastases

  • Patients with previously treated brain metastases are eligible, provided they are not accompanied by seizures and a baseline brain MRI scan demonstrates no current evidence of brain metastases
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 12 weeks
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• AST and ALT =< 2.5 times upper limit of normal (ULN) (=< 5 times ULN if liver metastases are present)
• Alkaline phosphatase =< 2.0 times ULN (=< 5 times ULN if bone or liver metastases are present)
• Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min
• Ability to understand and the willingness to sign a written informed consent document
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to, during, and for 3 months after completion of study treatment
• Must be able to reliably tolerate and/or receive oral medications

• No history of allergic reactions attributed to the following:

  • Camptothecin derivatives (e.g., topotecan hydrochloride, irinotecan hydrochloride, or exatecan mesylate)
  • Any ingredients contained within the liquid irinotecan hydrochloride solution (e.g., sorbitol)
  • Any antiemetics or antidiarrheals appropriate for administration with study therapy (e.g., loperamide or dexamethasone)
• No prior history of seizures

• No uncontrolled intercurrent illness including, but not limited to:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situations that would limit compliance with study requirements
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• More than 3 weeks since prior minimal radiotherapy (i.e., =< 5% of total marrow volume)
• More than 4 weeks since prior radiotherapy (i.e., > 5% of total marrow volume)
• No prior radiotherapy to >= 50% of total marrow volume

• Histologically or cytologically confirmed metastatic or unresectable malignancy meeting 1 of the following criteria:

  • Standard curative or palliative measures do not exist or are no longer effective
  • Irinotecan hydrochloride is considered to be a viable therapy regimen
• Patients enrolled on the expansion portion of the study will consist of two cohorts: those patients who are triple-negative, BRCA-mutant positive and those patients who have triple-negative, non-BRCA mutated breast cancer
• Patients with solid hematologic malignancies (Hodgkin or non-Hodgkin lymphoma) are eligible provided a bone marrow has been performed within 6 weeks of treatment
• Measurable disease per RECIST guidelines
• Patients must be negative for carrying the UGT1A1*28 allele (also called (TA)7)
• More than 4 weeks since prior experimental (i.e., non-FDA approved) therapy or immunotherapy and recovered
• Males receiving treatment for prostate cancer must be maintained at castrate levels of testosterone by continuation of luteinizing-releasing hormone agonists
• No cytochrome P450 CYP3A4 isoform-inducing drugs (e.g. phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, ketoconazole, St. John's Wort)
• No other investigational agents within 4 weeks of study entry
• No chronic growth factor support (e.g., filgrastim [G-CSF], pegfilgrastim) for maintenance of white blood cell counts or granulocyte counts
• No other concurrent anticancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) except medications for supportive care that may potentially have an anticancer effect (i.e., megestrol acetate, bisphosphonates) started 1 month prior to study
• Patients with active seizure or a history of seizure are excluded
• Patients with known active brain metastases should be excluded from this clinical trial; patients with prior treated brain metastases are allowed, providing that they were not accompanied by seizures and that a baseline brain MRI scan prior to study entry demonstrates no current evidence of brain metastases; all patients with CNS metastases must be stable for > 3 months after treatment and off steroid treatment prior to study enrollment