Oncolytic Adenovirus Ad5-DNX-2401

PRIMARY OBJECTIVES: I. To determine the maximal tolerated dose (MTD) of allogeneic bone marrow-derived human mesenchymal stem cells (BM-hMSCs) loaded with the oncolytic adenovirus DNX-2401 (BM-hMSCs-DNX2401) administered by intra-arterial injection (i.e., transfemoral endovascular intracranial injection) in patients with recurrent glioblastoma (GBM), IDH-mutant astrocytoma grade 4, gliosarcoma, or wild-type IDH-1 anaplastic astrocytoma. II.

To determine the local and systemic toxicity of allogeneic BM-hMSCs-DNX2401 administered by intra-arterial injection (i.e., transfemoral endovascular intracranial injection) in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma. III.

This phase I trial studies best dose and side effects of oncolytic adenovirus DNX-2401 in treating patients with high-grade glioma that has come back (recurrent). Oncolytic adenovirus DNX-2401 is made from the common cold virus that has been changed in the laboratory to make it less likely to cause an infection (such as a cold). The virus is also changed to target brain cancer cells and attack them.

Live record on ClinicalTrials.gov →

• Subjects must meet the following inclusion criteria to be eligible and enroll:
• Subjects must be willing and able to provide informed consent, undergo and comply with all study assessments, and adhere to the protocol schedule.
• Patients with recurrent malignant GBM or gliosarcoma will be eligible. Patients with recurrent anaplastic astrocytoma with wild-type IDH-1 gene will also be eligible if there is a significant enhancing mass on MRI (≥1.0 cm in diameter with upper limit of 5 cm maximal diameter) because their prognosis/behavior is similar to GBM. Subjects with an initial diagnosis of an IDH-mutant grade 2 or 3 astrocytoma are also eligible at recurrence if a biopsy at recurrence is determined to be IDH-mutant grade 4 astrocytoma, and there is a significant enhancing mass on MRI (≥1.0 cm in diameter with upper limit of 5 cm maximal diameter). A pathology report constitutes adequate documentation of histology for study inclusion.
• Patients must show unequivocal evidence for tumor recurrence or progression by MRI scan after failing prior surgical resection, biopsy, chemotherapy or radiation. A baseline MRI must be performed within 24 days prior to registration. Biopsy is encouraged at the time of recurrence if it is unclear that there is recurrent tumor. However, biopsy is not required if the practicing physician thinks that there is adequate radiographic and clinical evidence for recurrence.
• Male or female patients ≥ 18 years of age.
• Patients must be able to undergo endovascular treatment based on Doppler studies showing ICA that is less than 50% occluded.

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.