A Phase I Study of ABT-888 in Combination With Temozolomide in Cancer Patients

Inclusion Criteria: Dose escalation and expanded safety cohorts * Evaluable disease, histologically confirmed malignancy (metastatic or unresectable) and standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective * ECOG Performance Score less than or equal to 2 * Adequate hematologic, renal and hepatic function * Normal sodium, calcium and magnesium levels * Voluntarily signed informed consent Expanded Safety Cohorts Only * Population: * Metastatic melanoma (MM) * Hepatocellular carcinoma (HCC) Child Pugh Category A and B classification only * BRCA deficient tumor status\*: advanced breast cancer (with soft tissue disease), or advanced ovarian cancer, or advanced primary peritoneal cancer, or advanced fallopian tube cancer\* \*Patients must have histologically or cytologically confirmed solid tumors with a positive genetic test result documenting BRCA 1 or BRCA 2 mutation status, to be considered eligible. * Serial tumor biopsies: Required for all subjects enrolled in one of the Expanded Low Dose Safety Cohorts. Exclusion Criteria: Dose Escalation and Expanded Safety Cohorts * Known central nervous system (CNS) metastases or CNS primary cancer. * Previous or current malignancies at other sites, except: adequately treated in situ carcinoma of cervix uteri; basal/squamous cell carcinoma of skin; previous malignancy considered cured. * Previous history or current seizure disorder. * Clinically significant and uncontrolled major medical condition(s) or any medical condition that places the subject at an unacceptably high risk for toxicities. * Transplant recipients and patients receiving combination anti-retroviral therapy for HIV due to the use of immunosuppressant therapies. * Lactating or pregnant female. * Chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy will not be allowed within either 4 weeks, or 5 half lives of a targeted therapy prior to study drug administration (Study Day 1). * Prior therapy with regimens containing dacarbazine (DTIC) or TMZ is not permitted. * Anti-cancer therapy is not permitted during the treatment portion of the study. * Hormone therapy, bisphosphonates or LHRH-agonists for prostate cancer are permitted prior to and during the study. * Significant adverse event or toxicity due to previous anti-cancer treatment that has not recovered to within one grade level (not to exceed Grade 2) of baseline. Expanded Safety Cohorts Only: * MM Only: Prior treatment with DNA damaging agents or cytotoxic chemotherapy including carboplatin, cisplatin, fotemustine, paclitaxel, vincristine, TMZ and DTIC. * Prior therapy with biologic agents (including IL-2, interferon, bevacizumab, vaccines and immunostimulants) and signal transduction inhibitors (including sorafenib, erlotinib, sutent and elesclomol) are allowed. Lower Dose Expanded Safety Cohorts Only * Anti-coagulant restrictions for subjects that have tumor biopsies.