Table 4.
Clinical trials on gene therapies for malignant brain gliomas.
| # | Identifier | Title | # of Pts. | Main Interventions | Study Phase | Status | State |
|---|---|---|---|---|---|---|---|
| 1 | NCT03657576 | Trial of C134 in Patients With Recurrent GBM | 24 | C134 | 1 | Not yet recruiting | U.S. |
| 2 | NCT03603405 | HSV-tk and XRT and Chemotherapy for Newly Diagnosed GBM | 62 | ADV/HSV-tk | 1–2 | Recruiting | U.S. |
| 3 | NCT03596086 | HSV-tk + Valacyclovir + SBRT + Chemotherapy for Recurrent GBM | 36 | ADV/HSV-tk | 1–2 | Recruiting | U.S. |
| 4 | NCT03576612 | GMCI, Nivolumab, and Radiation Therapy in Treating Patients With Newly Diagnosed High-Grade Gliomas | 52 | AdV-tk | 1 | Recruiting | U.S. |
| 5 | NCT03491683 | INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) | 52 | INO-5401 | 1–2 | Active, not recruiting | U.S. |
| 6 | NCT03383978 | Intracranial Injection of NK-92/5.28.z (HER2.taNK) Cells in Patients With Recurrent HER2-positive Glioblastoma (Quilt 3.C001) | 30 | NK-92/5.28.z (HER2.taNK) | 1 | Recruiting | GE |
| 7 | NCT03283631 | Intracerebral EGFR-vIII CAR-T Cells for Recurrent GBM | 24 | EGFRvIII-CARs | 1 | Suspended | U.S. |
| 8 | NCT02844062 | Pilot Study of Autologous Anti-EGFRvIII CAR T Cells in Recurrent Glioblastoma Multiforme | 20 | anti-EGFRvIII CAR T cells | 1 | Recruiting | CH |
| 9 | NCT02664363 | EGFRvIII CAR T Cells for Newly-Diagnosed WHO Grade IV Malignant Glioma | 3 | EGFR vIII CAR T cells | 1 | Active, not recruiting | U.S. |
| 10 | NCT02340156 | Phase II Study of Combined Temozolomide and SGT-53 for Treatment of Recurrent Glioblastoma | 26 | SGT-53 | 2 | Recruiting | U.S. - TA |
| 11 | NCT02062827 | Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma | 36 | M032 (NSC 733972) | 1 | Recruiting | U.S. |
| 12 | NCT02031965 | Oncolytic HSV-1716 in Treating Younger Patients With Refractory or Recurrent High Grade Glioma That Can Be Removed By Surgery | 2 | oncolytic HSV-1716 | 1 | Terminated | U.S. |
| 13 | NCT01811992 | Combined Cytotoxic and Immune-Stimulatory Therapy for Glioma | 19 | Dose Escalation of Ad-hCMV-TK and Ad-hCMV-Flt3L | 1 | Active, not recruiting | U.S. |
| 14 | NCT01454596 | CAR T Cell Receptor Immunotherapy Targeting EGFRvIII for Patients With Malignant Gliomas Expressing EGFRvIII | 18 | Anti-EGFRvIII CAR transduced PBL | 1–2 | Completed | U.S. |
| 15 | NCT01269424 | BG & TMZ Therapy of Glioblastoma Multiforme | 10 | MGMTP140K-encoding retroviral vector | 1 | Terminated | U.S. |
| 16 | NCT01205334 | Administration of CMV-Specific Cytotoxic T Cells in Patients With Glioblastoma Multiforme | 2 | Autologous CMV-specific CTL | 1–2 | Terminated | U.S. |
| 17 | NCT01172964 | A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas | 15 | flucytosine | 1 | Completed | U.S. |
| 18 | NCT01156584 | A Study of a Retroviral Replicating Vector Combined With a Prodrug Administered to Patients With Recurrent Malignant Glioma | 54 | Toca 511 vector | 1 | Completed | U.S. |
| 19 | NCT01109095 | CMV-specific Cytotoxic T Lymphocytes Expressing CAR Targeting HER2 in Patients With GBM | 16 | HER.CAR CMV-specific CTLs | 1 | Completed | U.S. |
| 20 | NCT00870181 | ADV-TK Improves Outcome of Recurrent High-Grade Glioma | 47 | ADV-TK/GCV | 2 | Completed | CH |
| 21 | NCT00751270 | Phase 1b Study of AdV-tk + Valacyclovir Combined With Radiation Therapy for Malignant Gliomas | 15 | AdV-tk | 1 | Completed | U.S. |
| 22 | NCT00634231 | A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors | 12 | AdV-tk | 1 | Active, not recruiting | U.S. |
| 23 | NCT00589875 | Phase 2a Study of AdV-tk With Standard Radiation Therapy for Malignant Glioma (BrTK02) | 52 | AdV-tk | 1 | Completed | U.S. |
| 24 | NCT00272870 | Treatment of Newly Diagnosed Brain Tumors With Chemotherapy and Radiation Using Cells Modified for Chemoprotection and an Experimental Drug to Decrease the Tumor Cell Resistance to Chemotherapy | 1 | MGMT P140K | 1 | Terminated | U.S. |
| 25 | NCT00004080 | Gene Therapy in Treating Patients With Recurrent or Progressive Brain Tumors | 21–42 | recombinant adenovirus-p53 SCH-58500 | 1 | Completed | U.S. |
| 26 | NCT00002824 | Gene Therapy in Treating Patients With Primary Brain Tumors | 18 | gene therapy | 1 | Completed | U.S. |
| 27 | NCT00004041 | Gene Therapy in Treating Patients With Recurrent Malignant Gliomas | 30 | Ad5CMV-p53 gene | 1 | Completed | U.S. |
| 28 | NCT00005796 | Combination Chemotherapy Plus Gene Therapy in Treating Patients With CNS Tumors | 10 | gene therapy | 1 | Completed | U.S. |
| 29 | NCT00031083 | Dose Escalation Study to Determine the Safety of IFN-Beta Gene Transfer in the Treatment of Grade III & Grade IV Gliomas | 35 | Interferon-beta | 1 | Suspended | U.S. |
Ad5CMV-p53 gene: a defective type-5 adenoviral vector contains a cytomegalovirus (CMV) promoter and expressing wtp53 gene; Ad-hCMV-Flt3L: a human serotype 5, replication-defective adenoviral vector contains a cytomegalovirus promoter and expressing the soluble, immune-mediated stimulatory gene human fms-like tyrosine kinase 3 ligand (Flt3L); Ad-hCMV-TK: a human serotype 5, replication-defective adenoviral vector contains a cytomegalovirus (CMV) promoter and expressing the herpes simplex virus thymidine kinase (HSV-TK) gene; ADV: adenovirus; ADV-TK/GCV: adenoviral vector carrying the herpes simplex virus thymidine kinase gene in combination with the prodrug ganciclovir; AdV-tk: adenoviruses (Ad) carrying the thymidine kinase (HSVtk) gene; Anti-EGFRvIII CAR transduced PBL: an anti-epidermal growth factor receptor variant III (EGFRvIII) chimeric T cell receptor (CAR) gene tranduced with peripheral blood lymphocytes (PBL); BG: 06-benzylguanine; CAR T: chimeric antigen receptor T-cell; CMV: cytomegalovirus; CNS: central nervous system; EGFRvIII: epidermal growth factor receptor variant III; GBM: glioblastoma; GMCI: gene mediated cytotoxic immunotherapy; HER.CAR CMV-specific CTLs: human cytomegalovirus (CMV)-specific; chimeric T cell receptor (CAR) gene; HER2.taNK: human epidermal growth factor 2 (HER2) target-activated natural killer cells (taNK cells); HER2: human epidermal growth factor receptor type II (HER); HSV-tk: herpes simplex virus thymidine kinase gene; M032 (NSC 733972): a second-generation oncolytic herpes simplex virus (oHSV); MGMT P140K: P140K mutant of human O(6)-methylguanine-DNA-methyltransferase (MGMT); SBRT: stereotactic body radiation therapy; SCH-58500: a weakened adenovirus that carries the p53 gene; SGT-53: nanocomplex designed for systemic, tumor-targeting delivery of the wt p53 gene; TMZ: temozolomide; WHO: World Health Organization; XRT: radiation therapy; U.S.: United States; GE: Germany; CH: China; TA: Taiwan.