Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors (PED-DNX2401)

May 21, 2026 updated by: Clinica Universidad de Navarra, Universidad de Navarra

Intratumoral DNX-2401 Administration for Recurrent and Refractory High Grade Brain Tumors in Pediatric and Young Adult Patients

The goal of this clinical trial is to learn if intratumoral administration of DNX-2401 works to treat recurrent and refractory high grade brain tumors in children and young adults. It will also learn about the safety of DNX-2401.

The main questions it aims to answer are:

  • Does a single intratumoral administration of DNX-2401 elicit tumor response and improve survival?
  • Is a single intratumoral administration of DNX-2401 safe and well tolerated?

Participants will:

  • Undergo surgery for tumor biopsy followed by a single intratumoral administration of DNX-2401
  • Visit the clinic periodically for checkups and tests

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Tumors of the central nervous system (CNS) represent approximately 20% of childhood cancers and are the leading cause of cancer-related mortality in children. Pediatric high-grade CNS tumors, including gliomas, ependymomas and embryonal CNS tumors (such as medulloblastomas, atypical teratoid/rhabdoid tumors [AT/RT], and embryonal tumors with multilayered rosettes [ETMR]), are associated with a particularly poor prognosis, with median survival after diagnosis often below two years. Despite current conventional treatments, the outcome has not improved, and significant morbidity with impaired quality of life is frequent in survivors. This scenario is even more discouraging at the time of tumor recurrence, where curative options are nonexistent. Therefore, there is a clear need to find novel and alternative therapeutic approaches to improve both survival and quality of life of these children.

In the past years, oncolytic virotherapy has emerged as a promising therapeutic strategy, as it replicates in and destroys only tumor cells while activating the patient's immune system. Among the described oncolytic viruses, DNX-2401, a genetically modified adenovirus type 5, has shown an excellent therapeutic effect in murine models of pediatric high-grade brain tumors, as well as in children with newly diagnosed DIPG. Preclinical studies have demonstrated that Delta-24-RGD, both alone and in combination with radiotherapy, is safe and results in a significant increase in survival in immunodeficient and immunocompetent murine models of pediatric high-grade gliomas, including DIPGs. Moreover, this therapeutic benefit was also validated in AT/RT and other embryonal CNS tumors, resulting in 70% of long-term survivors and a reduction in the dissemination of these tumors. In the clinical setting, intratumoral administration of DNX-2401 has demonstrated to be safe and effective in several phase 1 and 2 clinical trials in adult patients with recurrent high-grade gliomas, both alone and with pembrolizumab, and in children with newly diagnosed DIPG in combination with radiotherapy.

This is an open-label phase 2 trial for pediatric and young adults patients, aged 1 to 25 years old, with three different types of high-grade brain tumors (high-grade gliomas including Diffuse Midline Gliomas, embryonal CNS tumors, and ependymomas), who have relapsed (i.e., tumors that return after treatment) or are refractory (i.e., do not respond to conventional treatment).

A Simon 2-stage optimal design will be used to maximize the probability of detecting the treatment's effectiveness, reducing the probability of continuing with it if it is not effective in the first stage. This statistical methodology will allow testing the null hypothesis that the true response rate is ≤20% versus the alternative hypothesis that the true response rate is ≥50%. A sample size of 13 patients per study group will be predetermined. A response (defined as complete response, partial response, or stable disease for at least 12 weeks) in at least 1 of 5 patients per study group in the first stage will be required for the study to be expanded to the second stage, and a response in 5 of 13 patients will be required to consider the treatment statistically positive.

The study participants will receive a single intratumoral dose of 5 x 10^10 viral particles of DNX-2401 in 1 mL of 0.9% sodium chloride, administered in the brain parenchyma via a SmartFlow Neuro Ventricular Cannula (ClearPoint Neuro) with neuronavigation guidance at a controlled rate over approximately 1 hour (67 minutes at a rate of 0.90 mL/hour). Before virus delivery, a stereotactic biopsy will be performed to obtain tumor tissue.

Clinical follow-up, including neurological examination, functional status and quality of life assessment will be performed at day 3 and during clinical visits at weeks 2, 4, 8, 12, 20, 28, 40 and 52 following DNX-2401 injection. Adverse events will be recorded using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5 tool for the first 12 weeks after experimental therapy. Postoperative MRI will be performed in all patients within 72 hours after surgery to detect the biopsy region and the DNX-2401 injection site. In the case of the preoperative Magnetic Resonnace Imaging (MRI), it will be considered the baseline MRI for response assessment, except in patients undergoing debulking surgery, in which early postoperative MRI will be considered the baseline MRI. Follow-up MRI will be performed at weeks 4, 8, 12, 20, 28, 40 and 52 following DNX-2401 injection.

Apart from the overall response rate, the treatment efficacy will also be measured in terms of survival, specifically using the following metrics: progression free survival (PFS) and overall survival (OS). PFS will be defined as the time from treatment to disease progression, determined either clinically or radiologically. OS will be defined as the time from treatment to patient death. Rates of PFS at 6- and 12-months will also be assessed as measures of outcome.

Tumor samples will be analyzed to characterize the immune tumor microenvironment and molecular composition. Blood, cerebrospinal fluid (when available), and microbiome samples will be collected longitudinally during follow-up visits to characterize viral kinetics and immune responses before and after DNX-2401 administration, and to explore correlations with clinical outcomes.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
39

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Jaime Gállego Pérez de Larraya, M.D., Ph.D.
  • Phone Number: +34 948 25 54 00
  • Email: jgallego@unav.es

Study Contact Backup

  • Name: Central Unit for Clinical Trials
  • Phone Number: +34 948 25 54 00
  • Email: ucicec@unav.es

Study Locations

  • Netherlands
      • Utrecht, Netherlands, 3584
  • Spain
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Recruiting
        • Cancer Center Clínica Universidad de Navarra
        • Contact:
          • Central Unit for Clinical Trials
          • Phone Number: +34 948 25 54 00
          • Email: ucicec@unav.es
        • Contact:
          • Jaime Gállego, M.D., Ph.D.
          • Phone Number: +34 948 25 54 00
          • Email: jgallego@unav.es

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • The participant or participant's parents or legally acceptable representatives (if applicable) provides written informed consent for the trial and the pediatric participant provides writ-ten assent, where applicable, based on age and country requirements.
  • Patients with recurrent or refractory high grade malignant brain tumors (high grade glioma, embryonal CNS tumors [medulloblastomas, ATRT, EMTR, pineoblastoma], and ependymomas) diagnosis based on initial histopathological diagnosis and further clinical and radiological fol-low-up, in whom gross total resection is not feasible, and with a life expectancy of at least 16 weeks at the time of consent.
  • Recurrences within the radiation field will be considered if there is confirmed growth of the lesion in two consecutive MRI or if they occur at least 12 weeks after completion of ra-diation therapy, or if there is clear histopathological confirmation of tumor recurrence.
  • Male and female participants age ≥ 1 years and ≤ 25 years.
  • A single measurable lesion longer than 10 mm in two perpendicular diameters, considered by the investigator to be accessible for safe stereotactic biopsy and virus injection.
  • Lansky Performance Status (LPS) ≥ 60 for participants < 16 years, or Karnofsky Performance Status (KPS) ≥ 60 for participants ≥ 16 years.
  • No other chemotherapy or immunotherapy in the 4 weeks before inclusion.
  • Steroids: free off or requiring decreasing or stable corticosteroid dose (≥ 0.05 mg/kg dexa-methasone daily, or equivalent for other steroids) in the 2 weeks before DNX-2401 admin-istration.
  • Radiation: no craniospinal irradiation, total body irradiation nor focal irradiation in the 6 weeks before inclusion.
  • Autologous Stem Cell Transplantation: patients must be ≥ 3 months post-transplant prior to entry of the study.
  • Patients must be fully recovered from all acute treatment related toxicities of all prior therapies.
  • Laboratory test: adequate hematological (platelets ≥ 100x10e9/L, neutrophils ≥ 1.0x10e9/L, hemoglobin ≥ 5,6 mmol/L), renal function (creatinine <1.5 times ULN) and liver function (≤3 times ULN) values.
  • Negative pregnancy test for female participants of child-bearing potential, where child-bearing potential is defined as a fertile female who is pubertal or post-pubertal and not permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy).
  • Female participants of child-bearing potential, who are sexually active, agree to use ac-ceptable birth control starting at informed consent and continuing for at least 120 days af-ter DNX-2401 administration. Male participants agree to use acceptable birth control start-ing at informed consent and continuing for at least 90 days after DNX-2401 administration.

Exclusion Criteria:

  • Any medical or psychological condition or disease that might interfere with the subject's ability to participate or give informed consent (if older than 16 years).
  • Spinal location, or lesions considered risky for stereotactic injection of virus or that might favor entrance of the virus in the ventricular system.
  • Any treatment outside the allowable guidelines outlined in the inclusion criteria.
  • Severe acute infection or intercurrent medical condition including, but not limited to se-vere renal, hepatic, heart or bone marrow failure that based on investigator discretion do not permit inclusion in the study.
  • Subjects with immunodeficiency or autoimmune conditions, active hepatitis or known HIV. No testing for Hepatitis B, Hepatitis C and HIV is required unless mandated by local health authority.
  • Subjects with another primary malignancy.
  • Prior history of encephalitis, multiple sclerosis or other CNS infections or primary CNS dis-ease that would interfere with evaluation.
  • Li Fraumeni Syndrome or a known germ line deficit in the retinoblastoma gene or its relat-ed pathways.
  • Concurrent therapy with any antiviral drug or any immunosuppressive drug (except ster-oids).
  • Life or life-attenuated vaccinations within 30 days prior to DNX-2401 administration and while participating in the study. Killed vaccines are permitted.
  • Prior participant in experimental viral therapy.
  • Inability to undergo MRI scans for any reason.
  • Pregnancy or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Single intratumoral infusion of DNX-2401
Single intratumoral infusion of 5 × 10^10 viral particles of DNX-2401 after tumor biopsy.
Biological: DNX-2401
Single intratumoral infusion of 5 × 10^10 viral particles of DNX-2401 after tumor biopsy.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Up to 52 weeks post-injection.
Percentage of patients achieving a Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) maintained for at least 12 weeks. Response is assessed according to the Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria.
Up to 52 weeks post-injection.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From treatment administration through week 12.
Number of participants with adverse events (AEs) as a measure of safety and tolerability. All AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).
From treatment administration through week 12.
Number of Participants With Serious Adverse Events (SAEs)
Time Frame: From treatment administration through week 12.
Number of participants with serious adverse events (SAEs) potentially related to DNX-2401.
From treatment administration through week 12.
Overall Survival (OS).
Time Frame: Up to 12 months.
Time from treatment administration to death from any cause.
Up to 12 months.
Progression-Free Survival (PFS).
Time Frame: Up to 12 months.
Time from treatment administration to the first documentation of objective tumor progression or death from any cause.
Up to 12 months.
Time to Best Overall Response
Time Frame: Up to 52 weeks.
Time from the date of DNX-2401 administration to the first documentation of the best objective response (Complete Response [CR], Partial Response [PR], or Stable Disease [SD] maintained for at least 12 weeks) according to RAPNO criteria.
Up to 52 weeks.
Duration of Overall Response
Time Frame: From the date of first documented response up to 52 weeks.
Time from the first documentation of objective response (CR, PR, or SD) to the first documentation of objective tumor progression (according to RAPNO criteria) or death from any cause.
From the date of first documented response up to 52 weeks.
Change From Baseline in Performance Status (Karnofsky/Lansky Score)
Time Frame: Baseline and weeks 2, 4, 8, 12, 20, 28, 40 and 52 following DNX-2401 injection.
Performance status will be assessed using the Karnofsky Performance Scale (for patients aged 16 years and older) or the Lansky Performance Scale (for patients younger than 16 years). Both scales range from 0 to 100, where 0 represents death and 100 represents normal activity. Higher scores indicate better functional status.
Baseline and weeks 2, 4, 8, 12, 20, 28, 40 and 52 following DNX-2401 injection.
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale Total Score.
Time Frame: Baseline and weeks 2, 4, 8, 12, 20, 28, 40 and 52 following DNX-2401 injection.
The PedsQL Generic Core Scale is a 23-item instrument. Each item is reversed-scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0). The total score is the sum of all items divided by the number of items answered. The total score ranges from 0 to 100, where 0 indicates poor quality of life and 100 indicates better quality of life.
Baseline and weeks 2, 4, 8, 12, 20, 28, 40 and 52 following DNX-2401 injection.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlative analysis
Time Frame: From baseline to month 12 following DNX-2401 injection.
To characterize the tumor immune microenvironment and molecular composition, the viral kinetics, the immune response to the treatment, and the fecal microbioma before and after DNX-2401 administration. Tumor samples and sequential blood and fecal samples (as well as cerebrospinal fluid samples, when available) will be analyzed, and correlated with clinical otucomes.
From baseline to month 12 following DNX-2401 injection.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Clinica Universidad de Navarra, Universidad de Navarra

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Princess Maxima Center for Pediatric Oncology
Asociación Española contra el Cáncer

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jaime Gállego Pérez de Larraya, M.D., Ph.D., Cancer Center Clínica Universidad de Navarra

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 12, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 5, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 13, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 20, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 21, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PED-DNX2401
  • 2024-515009-24-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data that underlie the results reported in publications arising from this study will be shared with qualified researchers or study collaborators.

IPD Sharing Time Frame

The IPD will be made available after publication of the primary results.

IPD Sharing Access Criteria

Access to de-identified individual participant data will be provided to qualified researchers upon reasonable request. Requests should be directed to the principal investigator.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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