Ignite Creation Date:
2026-03-26 @ 3:15 PM
Ignite Modification Date:
2026-03-30 @ 4:14 AM
Study NCT ID:
NCT07424092
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-02-20
First Post:
2026-02-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors
Sponsor:
Clinica Universidad de Navarra, Universidad de Navarra
Organization:
Study Overview
Official Title:
Intratumoral DNX-2401 Administration for Recurrent and Refractory High Grade Brain Tumors in Pediatric and Young Adult Patients
Status:
NOT_YET_RECRUITING
Status Verified Date:
2026-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PED-DNX2401
Brief Summary:
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
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
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.
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2024-515009-24-00 | CTIS | None | View |