CLINICAL TRIAL: A PHASE I STUDY IN ADVANCED SOLID MALIGNANCIES (NCI 7967)

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABT-888 is an orally available, small molecule inhibitor of poly(ADP-ribose) polymerease (PARP). PARP is an essential nuclear enzyme that plays a role in recognition of DNA damage and facilitation of DNA repair. Therefore, inhibition of PARP is expected to enhance the effects of DNA damage. Expression of PARP is higher in tumor cells as compared to normal cells. This overexpression has been linked to drug resistance and the ability of tumor cells to withstand genotoxic stress. It is anticipated that PARP inhibitors will function as sensitizing agents for chemotherapy and radiation therapy that are designed to cause DNA damage. The primary objective of the study is to determine the recommended dose for Phase 2 studies of ABT-888 that can be administered in combination with carboplatin and paclitaxel in patients who have advanced solid malignancies.