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.