This early phase I trial studies the effect of PARP inhibition on cellular and molecular changes in patients with ovarian cancer or triple-negative breast cancer. PARPs are proteins that help repair deoxyribonucleic acid (DNA) mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. The purpose of this study is to learn about mechanisms that may enable “PARP” to regulate and produce a response in breast and ovarian cancer. Findings from this study may enable future studies to offer targeted therapy to patients with breast or ovarian cancer.
Additional locations may be listed on ClinicalTrials.gov for NCT04041128.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. Measure DNA damage (gammaH2AX), apoptosis (caspase-3 cleavage) and homologous recombination (HR) (RAD51 foci) in tumor specimens after treatment with a PARP inhibitor.
II. Characterize the changes in adenosine diphosphate (ADP) ribosylated proteome that occurs due to treatment with a PARP inhibitor.
III. Correlate the “response” (as measured by DNA damage and apoptosis) and changes in the ADP ribosylated proteome (using novel ADP-ribose detection reagents developed in the Kraus lab and mass spectrometry) with the addition of the PARP inhibitor, at the time of surgery.
OUTLINE:
Patients undergo collection of tissue samples then receive olaparib orally (PO) twice daily (BID) for 7 days in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery or a second collection of tissue samples the day after the last dose of olaparib.
After completion of study, patients are followed up every 3-6 months for 2 years.
Lead OrganizationUT Southwestern/Simmons Cancer Center-Dallas
Principal InvestigatorJayanthi S. Lea
