A Biomarker-Guided Phase 2 Study of DB107-RRV (Retroviral Replicating Vector) Combined With DB107-Flucytosine Extended-Release Tablets in Patients With Recurrent Glioblastoma or Anaplastic Astrocytoma
The purpose of this study is to determine if the investigational products, DB107-RRV and DB107-FC, as a combination treatment will shrink high-grade glioma (HGG) in patients with recurrent/progressive, resectable or unresectable disease and increase the time that disease is controlled.
• Patients 18-75 years old.
• Histologically proven HGG that have recurred/progressed (first or second recurrence).
• Patients with unresectable or resectable HGG (AA or GBM) will be enrolled.
• Measurable disease on MRI as evidenced by 1 cm on two separate dimensions on MRI fluid attenuated inversion recovery (FLAIR) (non-enhancing) or contrast-enhancement.
• Last temozolomide dosage 4 weeks prior to surgery.
• Patients with prior radiation therapy are allowed, but histological tumor diagnosis of recurrent tumor must be confirmed according to the RANO criteria. Recurrence must be confirmed by diagnostic biopsy with local pathology review or contrast-enhanced MRI. If first recurrence of GBM is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiotherapy treatment field.
• Presence of Denovo Genomic Marker 7 (DGM7) biomarker in blood.
• Laboratory values (Platelet count ≥ 80,000, hemoglobin \[Hg\] ≥10 g/dL, absolute neutrophil count (ANC) \> 1,500 cells/mm3, absolute lymphocyte count (ALC) \> 500/mm3) and adequate liver function, total bilirubin\< 1.5 upper limit of normal (ULN), alanine transaminase (ALT) \<2.5 ULN. Estimated glomerular filtration rate (eGFR) should be \> 50 mL/min (Cockcroft Gault Formula). Patients with aspartate transaminase (AST) or ALT values \>3 ULN and total bilirubin \>1.5 mg/dL will be excluded.
• Patients cannot be pregnant at the time of enrollment or during the study. Patients willing to use one (1) effective method of contraception in addition to barrier methods (condoms) from the time of signing the informed consent form until 12 months after receiving the last dose of DB107-RRV or until there is no evidence of DB107-RRV in their blood, whichever is longer.
⁃ Karnofsky Performance Score (KPS) ≥ 70.
⁃ Patient is able to consent and abide by protocol.