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 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.
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.
Single group
DNX-2401
Biological/VaccineSingle intratumoral infusion of 5 × 10\^10 viral particles of DNX-2401 after tumor biopsy.
Overall Response Rate (ORR)
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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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).
Number of Participants With Serious Adverse Events (SAEs)
Number of participants with serious adverse events (SAEs) potentially related to DNX-2401.
Overall Survival (OS).
Time from treatment administration to death from any cause.
Progression-Free Survival (PFS).
Time from treatment administration to the first documentation of objective tumor progression or death from any cause.
Correlative analysis
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.
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Clinica Universidad de Navarra, Universidad de Navarra
Lead sponsor
Princess Maxima Center for Pediatric Oncology
Collaborator
Asociación Española contra el Cáncer
Collaborator
