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

NCT06606990 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: NCI-2024-07701IRB002354IRB00232510667
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• RAD51 response

  Will be defined as at least 5 percent of cells with at least 5 positive foci per nucleus. Will target a 30% Rad51 response rate. Will be compared descriptively across the 2 cohorts, with and without homologous repair deficiency mutations.

  Up to 3 years

Secondary Outcomes (4)

• Incidence of adverse events

  Up to 3 years

• Overall response

  From the time measurement criteria are met for complete response or partial response until the first date that recurrent or progressive disease is objectively documented; assessed up to 3 years

• Pharmacokinetics (PK)

  At baseline, post-infusion on cycle (C) 1 day (D) 1, before the biopsy on C1D2, pre-infusion and post-infusion C1D8, and C1D15

• Deoxyribonucleic acid (DNA) damage and repair signaling markers

  Up to 3 years

Other Outcomes (1)

• Genomic alterations

  Up to 3 years

Study Arms (1)

Treatment (pidnarulex)

EXPERIMENTAL

Patients receive pidnarulex 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 CT or MRI, biopsy, and collection of blood samples throughout the trial. Patients may undergo ECHO at screening and then as clinically indicated.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Biological: Pidnarulex

Interventions

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (pidnarulex)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (pidnarulex)

Pidnarulex BIOLOGICAL

Given IV

Also known as: CX-5461, CX5461, Pol I Inhibitor CX5461, RNA Pol I Inhibitor CX5461

Treatment (pidnarulex)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (pidnarulex)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (pidnarulex)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (pidnarulex)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed solid tumors with metastatic disease that have progressed after ≥ 1 line of prior therapy and/or for whom no standard treatment is available that has been shown to improve survival.
• Patients must have a molecular testing report to assess HRD mutation status prior to enrollment.
• Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, with at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest x-ray or as ≥ 10 mm (≥ 1 cm) with CT scan, MRI, or calipers by clinical exam).
• Patients must have a tumor site amenable to biopsy.
• Age ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky ≥ 70%).
• Absolute neutrophil count ≥ 1,500/mcL.
• Hemoglobin ≥ 9 g/dL.
• Platelets ≥ 100,000/mcL.
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
• (However, patients with known Gilbert disease who have serum bilirubin level of up to 3 mg/dl may be enrolled).
• International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 institutional upper limit of normal (ULN).
• Subjects may receive supplementation to meet this eligibility criteria.
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN.
• (AST and/or ALT ≤ 5 x ULN for patients with liver involvement).

You may not qualify if:

• Patients must have recovered from clinically-significant adverse-events of their most recent cancer immunotherapy to grade 1 or less (with the exception for alopecia or lymphopenia).
• Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of pidnarulex will be determined based on their potential to interact with the CYP3A4 isozyme. Specifically, subjects taking strong CYP3A4 inhibitors or strong CYP3A4 inducers will be excluded from participation in the trial. A list of agents that interact with CYP450 isoenzymes is provided. For medications or substances not listed, or in cases of uncertainty, the principal investigator may consult with a medical expert or a pharmacologist to make an informed decision regarding eligibility.
• History of allergic reactions attributed to inactive ingredients in the drug product.
• Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous.
• Patients with cirrhosis, regardless of the etiology, will be excluded from participation in the trial. This is due to the increased risk of complications and adverse events associated with the study medication in this population.
• Presence of known photosensitivity disorders (xeroderma pigmentosa, porphyria etc.). Patients who do not agree to use sunglasses and sun blocker (with sun protection factor 50 \[SPF50\] to ultraviolet B \[UVB\] and a high degree of protection against ultraviolet A \[UVA\]) if exposed to sunlight during the course of the study and for 3 months after the last dose are not eligible. Appropriate sunscreen products will be provided. Patients who plan to use sun beds or tanning booths during the course of the study and within 3 months after the last dose are not eligible.
• Active ocular surface disease at baseline (based on ophthalmological evaluation).
• History of cicatricial conjunctivitis (as evaluated by an ophthalmologist).

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; CX 5461

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Jibran Ahmed

  National Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2024
• First Posted: September 23, 2024
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)