Table 4.
Clinical trials of gene therapy for brain tumours
| Study | Study status |
Vector | Transgene | Route of administration |
Efficacy |
|---|---|---|---|---|---|
| Papanastassiou et al. (2002)127 |
Phase I | HSV-1 (1716 strain) |
Wild-type replication-competent virus |
Intratumoural | 25% of patients disease-free for 15–22 months |
| Chiocca et al (2004)128 |
Phase I | Adenovirus (ONYX-015) |
Wild-type replication-competent virus |
Resection cavity | No signifcant difference in patient survival |
| Forsyth et al (2008)129 |
Phase I | Reovirus | Wild-type replication-competent virus |
Intratumoural | 8% of patients disease-free for >6 months |
| Markert et al (2000)134 |
Phase I | HSV-1 (G207 strain) |
Wild-type replication-competent virus |
Intratumoural | 29% of patients with improved neurological status, 38% with decreased tumour volume on MRI |
| Rampling et al (2000)135 |
Phase I | HSV-1 (1716 strain) |
Wild-type replication-competent virus |
Intratumoural | 33% of patients with decreased tumour volume on MRI, 56% with stable tumour volume on MRI |
| Freeman et al (2006)136 |
Phase I–II | Newcastle disease virus (HUJ strain) |
Wild-type replication-competent virus |
Intravenous | 7% of patients with complete response, 21% long-term survivors (range 61–66 weeks) |
| Ram et al (1997)114 |
Phase I | Retrovirus | HSV-1–thymidine kinase | Intratumoural | Modest antitumour activity in 27% of patients, 7% recurrence-free for 50 months |
| Izquierdo et al (1996)115 |
Phase I | Retrovirus | HSV-1–thymidine kinase |
Intratumoural | No significant difference in patient survival |
| Palu et al (1999)139 |
Phase I | Retrovirus | HSV-1–thymidine kinase/IL-2 |
Intratumoural | 25% of patients showed >50% reduction in tumour volume on MRI |
| Chiocca et al (2011)138 |
Phase Ib | Retrovirus | HSV-1–thymidine kinase |
Resection cavity | 2-year survival 33%, 3-year survival 25% |
| Shand et al (1999)116 |
Phase I–II | Retrovirus | HSV-1–thymidine kinase |
Resection cavity | 15% of patients showed stable tumour volume by MRI at >7 months |
| Klatzmann et al (1998)117 |
Phase I–II | Retrovirus | HSV-1–thymidine kinase |
Resection cavity | Median survival 17.4 months, 25% of patients showed stable tumour volume on MRI at >4 months |
| Prados et al (2003)118 |
Phase I–II | Retrovirus | HSV-1–thymidine kinase |
Resection cavity or intraventricular | Median survival 8.4 months |
| Immonen et al (2004)122 |
Phase IIb | Retrovirus | HSV-1–thymidine kinase |
Resection cavity | Median survival prolonged from 37.7 weeks to 62.4 weeks |
| Rainov (2000)109 |
Phase III | Retrovirus | HSV-1–thymidine kinase |
Resection cavity | No significant difference in patient survival |
| Trask et al (2000)120 |
Phase I | Adenovirus | HSV-1–thymidine kinase |
Intratumoural | 2-year survival in 25% of patients |
| Germano et al (2003)121 |
Phase I | Adenovirus | HSV-1–thymidine kinase |
Resection cavity | Median survival 59 weeks |
| Smitt et al (2003)155 |
Phase I | Adenovirus | HSV-1–thymidine kinase |
Resection cavity | No objective radiological response |
| Chiocca et al (2008)125 |
Phase I | Adenovirus | IFN-β | Intratumoural | Median survival 17.9 weeks, median progression-free survival 9.3 weeks |
| Lang et al (2003)126 |
Phase I | Adenovirus | p53 | Intratumoural | Median survival 10 months, 7% of patients recurrence-free at 3 years |
| Sandmair et al (2000)123 |
Phase IIa | Adenovirus | HSV-1–thymidine kinase | Resection cavity | Median survival 15 months versus 8.3 months in controls |
Abbreviation: HSV-1, herpes simplex virus type 1.