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Metastatic Malignant Solid NeoplasmPhase 1NCT06606990

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

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Malignant Solid Neoplasm
What is being tested?
Biopsy Procedure, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
1 Jul 2025to 31 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%).
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  • 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).
  • Potassium ≥ lower limit of normal (LLN).
  • Subjects may receive supplementation to meet this eligibility criteria.
  • Magnesium ≥ LLN.
  • Subjects may receive supplementation to meet this eligibility criteria.
  • Ionized or corrected calcium ≥ LLN.
  • Subjects may receive supplementation to meet this eligibility criteria.
  • Creatinine ≤ 1.5 x institutional ULN OR creatinine clearance levels ≥ 60 ml/min based on the Cockcroft-Gault formula.
  • Oxygen (O2) saturation > 90% on room air.
  • Prior standard or investigational therapy must have been completed ≥ 4 weeks or ≥ 5 half-lives of the prior agent (whichever is shorter) prior to enrollment; the exception is ≥ 2 weeks since any investigational agent administered (at a sub-therapeutic dose) as part of a phase 0 study.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable.
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured.
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for ≥ 1 month after treatment of the brain metastases.
  • Patients with a prior or concurrent malignancy are eligible for this trial if, in the judgement of the principal investigator, the malignancy and its treatment do not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
  • The effects of pidnarulex on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) 14 days prior to study entry and for the duration of study participation and for at least 6 months after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women should not breastfeed while taking pidnarulex and for 6 months after cessation of treatment. Men treated or enrolled on this protocol must also agree to use adequate contraception 14 days prior to the study, for the duration of study participation, and 6 months after completion of pidnarulex administration.
  • Willingness to provide blood and biopsy samples for research purposes.
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Who cannot join

  • 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.
  • Pregnant and lactating women are excluded from this trial. The exclusion is based on the potential risk of adverse effects of pidnarulex on fetal development and newborn health. The safety of pidnarulex has not been established in pregnant or lactating women, and there is a possibility that the drug could cause harm to the developing fetus or be transferred to the infant through breast milk. Additionally, the physiological changes that occur during pregnancy and lactation could alter the pharmacokinetics and pharmacodynamics of pidnarulex, leading to unpredictable drug exposure and efficacy.
  • Patients with chronic, active HBV or HCV infections that require ongoing antiviral treatment will be excluded from the trial. This exclusion is due to the potential for drug interactions with the study medication and the risk of exacerbating liver disease.
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  • 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).

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • National Cancer Institute Developmental Therapeutics Clinic

    Bethesda, Maryland, 20892

    Site Public Contact, 800-411-1222

    A P. Chen

    Recruiting

Other trials in United States

About this study

Official title: Pilot Study of Pidnarulex Pharmacodynamics in Patients With Advanced Solid Tumors

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Biopsy Procedure, Biospecimen Collection, Computed Tomography, Echocardiography Test, Magnetic Resonance Imaging
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • PidnarulexBiological

    Also called CX-5461, CX5461, Pol I Inhibitor CX5461, RNA Pol I Inhibitor CX5461

    Given IV

Study groups in NCT06606990
Study groupRoleWhat they receive
Treatment (pidnarulex)ExperimentalPatients 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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Biological: Pidnarulex

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 3 years

Secondary outcomes (4)

  1. Incidence of adverse events

    Will be summarized using Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 3 years

  2. Overall response

    Measured: 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

  3. Pharmacokinetics (PK)

    PK will be measured using plasma.

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

  4. Deoxyribonucleic acid (DNA) damage and repair signaling markers

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2024
  2. Study start1 Jul 2025
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06606990
Sponsor's protocol ID
NCI-2024-07701
Other IDs
NCI-2024-07701, IRB002354, IRB002325, 10667, 10667
Status last verified
Sep 2026
First submitted
20 Sep 2024
Last updated
16 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

RAD51 response (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06606990.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.

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