A Phase 1 Study of the Polymerase Theta (POLθ) Inhibitor Novobiocin in BRCA- Mutant and Other DNA Damage Repair-Deficient Solid Tumors
National Cancer Institute (NCI)
Summary
This phase I trial tests the safety, side effects, and best dose of novobiocin in treating cancer patients with alterations in deoxyribonucleic acid (DNA) repair genes. Novobiocin is an antibiotic that blocks the activity of a protein called DNA polymerase theta, which helps repair DNA that has become damaged as cells grow and divide. Cancer cells that cannot repair their damaged DNA die. This medication may help shrink or stabilize cancer with a mutation in DNA repair genes.
Description
PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of novobiocin sodium (novobiocin) administered on a 5-days on/2-days off schedule in patients with solid tumors carrying homologous recombination (HR) or DNA damage repair (DDR) alterations that are poly (ADP-ribose) polymerase (PARP) inhibitor-naïve or -resistant. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate the safety and tolerability of novobiocin administered on a 5-days on/2-days off schedule in patients with solid tumors carrying HR or DDR alte…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective * Patients must have histologically confirmed solid tumor with a known pathogenic mutation in BRCA1/2, PALB2, RAD51C, RAD51D, ATM, BARD1, BLM, BRIP1, CDK12, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, NBN (NBS1), RAD50 and RAD51B as confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified method. Patients with alterations defined only by germline testing are eligib…
Interventions
- ProcedureBiopsy Procedure
Undergo tumor biopsy
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureDiagnostic Imaging Testing
Undergo medical imaging scans
- BiologicalNovobiocin Sodium
Given PO
Locations (23)
- City of Hope Comprehensive Cancer CenterDuarte, California
- UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory CareIrvine, California
- UC San Diego Moores Cancer CenterLa Jolla, California
- Los Angeles General Medical CenterLos Angeles, California
- USC / Norris Comprehensive Cancer CenterLos Angeles, California
- UC Irvine Health/Chao Family Comprehensive Cancer CenterOrange, California