Table 2.
Clinical trials of gene therapy for glioblastoma and other malignant brain tumors in the United States*
| Clinical Trial Identifier | Trial Phase | Therapeutic Agent | Delivery Mechanism | Therapeutic Strategy | Type(s) of Cancer |
|---|---|---|---|---|---|
| NCT01156584 | I/II | Toca-511 carrying CD + 5-FC | RRV | Suicide gene + viral oncolysis | Recurrent HGG |
| NCT01470794 | I | Toca-511 carrying CD + 5-FC | RRV | Suicide gene + viral oncolysis | Resection cavity of recurrent or progressive grade III or IV astrocytic tumors |
| NCT01985256 | I | Toca-511 carrying CD + 5-FC | RRV given intravenously | Suicide gene + viral oncolysis | Recurrent or progressive grade III or IV astrocytic tumors |
| NCT01174537 | I/II | Newcastle Disease Virus | Replicating virus | Viral oncolysis | GBM, gliosarcoma, and neuroblastoma |
| NCT01301430 | I/II | H-1 parvovirus (ParvOryx-01) | Replicating virus | Viral oncolysis | GBM |
| NCT01491893 | I | Engineered chimeric poliovirus (PVS-RIPO) | Replicating virus | Viral oncolysis + immune activation | GBM and recurrent supratentorial GBM |
| NCT00390299 | I | Measles virus derivative (MV-CEA) | Replicating virus | Viral oncolysis + immune activation | Recurrent GBM |
| NCT02062827 | I | HSV-1 expressing IL-12 (M032) | Replicating virus | Viral oncolysis + antiangiogenesis | Recurrent/progressive GBM, anaplastic astrocytoma, or gliosarcoma |
| NCT01582516 | I/II | AdV-delta-24-RGD | Replicating virus delivered via CED | Viral oncolysis | Recurrent GBM |
| NCT00805376 | I | DNX2401 (formerly known as Delta-24-RGD-4C) | Replicating virus | Viral oncolysis | Recurrent malignant gliomas |
| NCT01956734 | I | DNX2401 (formerly known as Delta-24-RGD-4C) + TMZ | Replicating virus | Viral oncolysis | First GBM recurrence |
| NCT02031965 | I | HSV-1716 | Replicating virus | Viral oncolysis | Recurrent childhood GBM and malignant glioma |
| NCT00589875 | IIa | AdV-tk + valacyclovir + radiation therapy | Nonreplicating virus | Suicide gene | Newly diagnosed malignant gliomas |
| NCT00634231 | I | AdV-tk + valacyclovir + radiation therapy | Nonreplicating virus | Suicide gene | Children with malignant glioma |
| NCT00751270 | Ib | AdV-tk + valacyclovir + radiation therapy | Nonreplicating virus | Suicide gene | Malignant gliomas |
| NCT01811992 | I | AdV-hCMV-TK & AdV-hCMV-Flt3L | Nonreplicating virus | Suicide gene + immune stimulation | Malignant glioma and GBM |
| NCT01260506 | I/II | VB-111 + bevacizumab | Nonreplicating virus given intravenously | Antiangiogenic | Relapsed GBM |
| NCT02026271 | I | Adenovirus vector expressing IL-12 (INXN-2001) + veledimex | Nonreplicating virus | Immune-mediated cell death | Recurrent/progressive GBM and grade III astrocytic tumor |
| NCT01172964 | Pilot | CD + 5-FC | Neural stem cells | Suicide gene | Recurrent HGG |
*The trials have active status (open, recruiting, or ongoing) as of September 2014.
Abbreviations: 5-FC, fluorocytosine; AdV, adenovirus; ALT, autologous lymphocyte transfer; CD, cytosine deaminase; CEA, carcinoembryonic antigen; CED, convection-enhanced delivery; CMV, cytomegalovirus promoter; Flt3L, FMS-like tyrosine kinase 3 ligand; GBM, glioblastoma; HER, human epidermal growth factor receptor 2; HGG, high-grade glioma; HSV, herpes simplex virus; IL, interleukin; MV, measles virus; RGD, Arg-Gly-Asp motif; RRV, retroviral replicating vector; TK, thymidine kinase; TMZ, temozolomide; VB-111, nonreplicating adenovector targeting Fas-Chimera transgene to angiogenic tumor blood vessels.