A Pharmacodynamics-Driven Trial of Talazoparib, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Aberrations in Genes Involved in DNA Damage Response
National Cancer Institute (NCI)
Summary
This phase II trial studies if talazoparib works in patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and has mutation(s) in deoxyribonucleic acid (DNA) damage response genes who have or have not already been treated with another PARP inhibitor. Talazoparib is an inhibitor of PARP, a protein that helps repair damaged DNA. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. All patients who take part on this study must have a gene aberration that changes how their tumors are able to repair DNA. This trial may help scientists learn whether some patients might benefit from taking different PARP inhibitors "one after the other" and learn how talazoparib works in treating patients with advanced cancer who have aberration in DNA repair genes.
Description
PRIMARY OBJECTIVE: I. Determine the pharmacodynamic (PD) effect of talazoparib in tumor biopsies for patients with aberrations in deoxyribonucleic acid (DNA) damage response genes who have or have not received prior PARP inhibitor treatment (separately). SECONDARY OBJECTIVE: I. Determine the response rate (complete response \[CR\] + partial response \[PR\]) of treatment with talazoparib in patients with aberrations in DNA damage response genes. EXPLORATORY OBJECTIVE: I. Investigate tumor genomic alterations potentially associated with sensitivity or acquired resistance to talazoparib. OU…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Adult patients with solid tumors and documented germline or somatic aberrations in genes involved in DNA damage response (DDR) and whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options. Molecular testing performed at an National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) (NCT02465060) study-designated Clinical Laboratory Improvement Act (CLIA) laboratory or at Myriad Genetics, GeneDx, Invitae, or the Frederick National Laboratory for Cancer Research (FNLCR) Molecular Characterizat…
Interventions
- ProcedureBiopsy Procedure
Undergo biopsy
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureComputed Tomography
Undergo CT scan
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- DrugTalazoparib
Given PO
Locations (4)
- UF Health Cancer Institute - GainesvilleGainesville, Florida
- National Cancer Institute Developmental Therapeutics ClinicBethesda, Maryland
- National Institutes of Health Clinical CenterBethesda, Maryland
- University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma