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.
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.
Histology other than GBM, gliosarcoma, IDH wild-type astrocytoma grade III or IDH-mutant astrocytoma grade 4.
Tumor foci detected below the tentorium or beyond the cranial vault.
Tumor within the posterior fossa.
Tumor with leptomeningeal spread.
Sequential
Oncolytic Adenovirus Ad5-DNX-2401
Biological/VaccineGiven IA
Therapeutic Conventional Surgery
Procedure/SurgeryUndergo surgery
Maximum-tolerated dose (MTD)
The MTD will be defined as the dose below the dose that results in greater than or equal to one-third of the subjects exposed who experienced grade 3 or 4 (except hematological, grade 4 required) toxicity according to National Cancer Institute Common Toxicity Criteria that is deemed to be at least "probably related" to the study drug (i.e., dose-limiting toxicity \[DLT\]).
Incidence of adverse events (AEs)
AEs will be summarized both overall and by dose group and tabulated by severity, relationship to BM-hMSCs-DNX 2401and causality. The number and percentage of subjects experiencing AEs will be tabulated by body system/preferred term both overall and by dose group. When an AE occurs more than once, the maximum severity and causality will be counted.
Tumor response
Will be based upon change in tumor size by serial magnetic resonance imaging scans post injection.
Time to progression
Virus replication in tumor
Detection of replicating delta-24-RGD-4C in tumor tissue will be done by immunohistochemistry against E1A protein and hexon protein.
Virus shedding
Polymerase chain reaction of serum, nasopharyngeal secretions, and urine will be performed.
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M.D. Anderson Cancer Center
Lead sponsor
DNAtrix, Inc.
Collaborator
