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
• 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.