scholarly journals Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial

Gene Therapy ◽  
2000 ◽  
Vol 7 (10) ◽  
pp. 867-874 ◽  
Author(s):  
J M Markert ◽  
M D Medlock ◽  
S D Rabkin ◽  
G Y Gillespie ◽  
T Todo ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Phase I ◽  
Malignant Glioma ◽  
Phase I Trial ◽  
Virus Mutant ◽  
Simplex Virus

Treatment of recurrent malignant glioma with G207, a genetically engineered herpes simplex virus-1, followed by irradiation: Phase I study results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2042-2042
Author(s):  
M. Karrasch ◽  
G. Y. Gillespie ◽  
E. Braz ◽  
P. G. Liechty ◽  
L. B. Nabors ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Phase I ◽  
Malignant Glioma ◽  
Phase I Study ◽  
Median Overall Survival ◽  
Recurrent Malignant Glioma ◽  
Simplex Virus

2042 Background: G207 is a doubly mutated (deletion of both γ134.5 loci, insertional inactivation of UL39) herpes simplex virus (HSV)-1. Safety and efficacy of intracerebral inoculations of G207 to patients suffering from recurrent malignant gliomas have been demonstrated in previous clinical trials. Methods: In this phase I clinical trial, a total of 1 x 109 plaque forming units (pfu) G207 were administered by five stereotactic injections of 0.2 mL each into regions of recurrent malignant glioma defined by MRI, followed by focal radiation therapy 24 hours post injection. Included patients suffered from inoperable pathologically proven recurrent glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) which was progressive despite radiotherapy or chemotherapy and failed external beam radiotherapy > 5 Gray prior to study enrolment. Results: 9 patients were treated in this phase I study. 5 patients were suffering from relapsed GBM, 4 patients were suffering from relapsed AA. 1 month after treatment, 3 patients (3xGBM) showed SD, 2 patients (1xGBM, 1xAA) PR, and 4 patients (1xGBM, 3xAA) PD. The 2 patients with initial PR (1xGBM, 1xAA) were re-treated with G207/Irradiation at time point of tumor recurrence, showing PR one month after re-treatment again. Median overall survival time for all 9 patients was 229 days (7.6 months), with one patient still alive at time of abstract submission. In patients suffering from relapsed GBM, mOS was 7.4 months, in patients suffering from relapsed AA, mOS was 9.25 months. 20 serious adverse events occurred in this study, only 3 were possible/probable related to G207/irradiation. Within persistent areas of tumor, HSV staining was present by using a polyclonal antibody for HSV, indicating intratumoral G207 replication (proof of concept). Conclusions: In 9 patients suffering from relapsed GBM or AA, stereotactic intracerebral G207 inoculation followed by radiation therapy was feasible, safe, and induced clinically relevant responses. G207/Irradiation re-treatment was possible and induced anew clinical responses. Median overall survival is superior to published data in this patient population. Therefore, further clinical development of G207 in GBM is medically reasonable. [Table: see text]

scholarly journals Treatment of Experimental Subcutaneous Human Melanoma with a Replication-Restricted Herpes Simplex Virus Mutant

1997 ◽  
Vol 108 (6) ◽  
pp. 933-937 ◽  
Author(s):  
Bruce P. Randazzo ◽  
Mulki G. Bhat ◽  
Santosh Kesari ◽  
Nigel W. Fraser ◽  
S. Moira Brown
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Human Melanoma ◽  
Virus Mutant ◽  
Simplex Virus

A phase I dose-escalation study of intratumoral herpes simplex virus-1 mutant HSV1716 in pediatric/young adult patients with refractory non-central nervous system solid tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10047-10047
Author(s):  
Timothy P. Cripe ◽  
John M Racadio ◽  
Joe Conner ◽  
Alexander Towbin ◽  
Marianne M Brunner ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Young Adult ◽  
Phase I ◽  
Viral Vectors ◽  
Adult Patients ◽  
Dose Escalation Study ◽  
Ct Guided ◽  
Antiviral Immune Response ◽  
Simplex Virus

10047 Background: HSV1716 is a mutant herpes simplex virus type 1 deleted in the RL1 gene which encodes the protein ICP34.5, a specific determinant of virulence. Mutants lacking the RL1 gene are capable of replication in actively dividing cells but not in terminally differentiated cells – a phenotype exploited to selectively kill tumor cells. Studies in adult patients with high grade glioma, melanoma and squamous cell carcinoma report that HSV1716 is safe when administered by intra-tumoral injection. This is the first study of HSV1716 in pediatric/young adult patients. Methods: The primary endpoint of the study is to assess safety of intratumoral HSV1716 in pediatric/young adult patients, and to determine any dose-limiting toxicities (DLT) at the doses given. Patients undergo long-term follow up in accordance with FDA guidelines for viral vectors. The secondary endpoints of the study are to measure: (i) antiviral immune response; (ii) systemic viremia and viral shedding and (iii) the antitumor activity of HSV1716 by radiological response within the confines of a Phase I study. Patients aged 7 to 30 with solid non-CNS tumors refractory to standard therapy (or for which no therapy exists) are eligible for the study provided the target lesion is accessible to image-guided injection. Eligible patients receive a single dose of HSV1716 (Virttu Biologics Limited) at either 105 or 2x106 plaque forming units (pfu) HSV1716 administered directly into the tumor via ultrasound or CT-guided injection by an interventional radiologist. Tumor response between baseline and day 28 is assessed by modified RECIST criteria. Patients showing at least stable disease may receive up to a 3 additional doses of HSV1716. Results: Recruitment of the first cohort of 3 patients has been completed without DLT or procedure related severe adverse events. In the second cohort, 2 patients have been treated without DLT or procedure related SAE. Conclusions: The trial is in progress and the study is open to recruitment. Clinical trial information: NCT00931931.

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