Phase 1 Study of Novobiocin, a Polymerase Theta Inhibitor, for Treating Solid Tumors with DNA Repair Gene Alterations including BRCA Mutations

What this Trial Is About

Researchers are evaluating the safety, side effects, and best dose of novobiocin in patients with solid tumors that have alterations in DNA repair genes. Novobiocin is an antibiotic that blocks a protein called DNA polymerase theta, which helps repair damaged DNA in cells. This study focuses on patients with tumors carrying specific gene mutations related to DNA repair, who may or may not have received prior PARP inhibitor treatment. Participants receive novobiocin orally once daily for 5 days followed by 2 days off each week, with treatment cycles repeating every 28 days if the disease does not progress or toxicity is unacceptable. Throughout the study, patients undergo tumor biopsies, medical imaging scans, and blood sample collection. After completing treatment, patients are followed up every 3 to 6 months for 2 years to monitor outcomes. During the trial, researchers monitor the maximum tolerated dose and recommend a phase 2 dose of novobiocin. They also assess anti-tumor activity, safety, tolerability, and pharmacokinetics. Additional analyses include genetic sequencing and gene expression studies on tumor biopsies. Outcome measures include radiological response, progression-free survival, duration of response, and biological effectiveness over up to 2 years of observation.

Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes