NCT06606990

Testing How the Body Responds to the Drug CX-5461 (Pidnarulex) in Patients With Metastatic Solid Cancers

Pilot Study of Pidnarulex Pharmacodynamics in Patients With Advanced Solid Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of pidnarulex (CX-5461) in treating patients with solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic). Pidnarulex is an oral inhibitor of ribonucleic acid polymerase I, with potential antineoplastic activity. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill cancer cells.

Detailed description

PRIMARY OBJECTIVE: I. To assess whether pidnarulex induces a Rad51 response, which will be determined by an integral biomarker of percentage of cells with Rad51 nuclear foci in tumor biopsy specimens in patients with and without homologous repair deficiency (HRD) genetic mutations. SECONDARY OBJECTIVES: I. To determine the safety and tolerability of pidnarulex. II. To determine the overall response rate (complete responses plus partial responses) in patients with advanced, refractory solid tumors. III. To measure the pharmacokinetics of pidnarulex. IV. To evaluate other DNA damage and repair signaling markers including Top2, G4 stabilization, RPA32, pSer33-RPA32, γH2AX, 53BP1, pSer8-RPA32, pKap1m and pNBS1. EXPLORATORY OBJECTIVE: I. To examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with response or resistance. OUTLINE: Patients receive pidnarulex intravenously (IV) over 60 minutes on days 1 and 8 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI), biopsy, and collection of blood samples throughout the trial. Patients may undergo echocardiography (ECHO) at screening and then as clinically indicated. After completion of study treatment, patients are followed up at 30 days.

Conditions

• Metastatic Malignant Solid Neoplasm

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Echocardiography Test	Undergo ECHO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
BIOLOGICAL	Pidnarulex	Given IV

Timeline

• Start date: 2025-07-01
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2024-09-23
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study