A Phase I Study of ABT-888 in Combination With Temozolomide (TMZ) in Subjects With Non-Hematologic Malignancies (NHM) and Metastatic Melanoma (MM)
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
- 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
*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
- Serial tumor biopsies: Required for all subjects enrolled in one of the Expanded Low
Dose Safety Cohorts.
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
- 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.