G207 for Brain Cancer

Recruiting at 2 trial locations

Overseen By Gregory K Friedman, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antivirals, Immunosuppressives

Disqualifiers: Pregnancy, HIV, Other malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 week

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a clinical trial to determine the safety of inoculating G207 (an experimental virus therapy) into a recurrent or refractory cerebellar brain tumor. The safety of combining G207 with a single low dose of radiation, designed to enhance virus replication, tumor cell killing, and an anti-tumor immune response, will also be tested. Funding Source- FDA OOPD

Will I have to stop taking my current medications?

The trial requires that you stop taking any drugs active against HSV (a type of virus) and any immunosuppressive drugs, except for dexamethasone or prednisone. If you are on other anticancer or investigational drugs, you will need to stop those as well.

What data supports the effectiveness of the treatment G207 for brain cancer?

Research shows that G207, a genetically engineered herpes simplex virus, can kill brain tumor cells and reduce tumor growth in animal models. In adult trials, about half of the patients showed a positive response, and preclinical studies suggest it is effective against various pediatric brain tumors. ^{1 2 3 4 5}

Is G207 safe for use in humans?

G207, a genetically engineered herpes simplex virus, has been tested in several clinical trials and shown to be generally safe in humans. No serious side effects directly linked to G207 were reported, and no patients developed herpes encephalitis (brain inflammation caused by the virus). ^{2 3 6 7 8}

How is the treatment G207 different from other brain cancer treatments?

G207 is a unique treatment for brain cancer because it uses a genetically engineered herpes simplex virus that selectively replicates in tumor cells, destroying them while sparing normal cells. This approach combines viral therapy with immunotherapy, potentially offering a novel way to target and eliminate brain tumors without the severe side effects of traditional treatments like chemotherapy and radiation. ^{1 2 3 8 9}

Research Team

Gregory Friedman, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for children and young adults aged 3 to less than 22 years with certain types of malignant cerebellar brain tumors that have returned or haven't responded to treatment. Participants must have stable vital functions, a specific performance score indicating they can perform daily activities, and a life expectancy of at least 8 weeks. They should not be on certain medications, have HIV, other cancers, or severe infections.

Inclusion Criteria

I have recovered from side effects of my previous cancer treatments.

My tumor is between 1.0 and 3.0 cm in size and can be operated on.

I've recovered from side effects of previous treatments and it's been over a week since my last dose, or over 3 months if it was viral therapy.

Exclusion Criteria

I was diagnosed with or am being treated for encephalitis, a CNS infection, or multiple sclerosis recently.

Pregnant or lactating females

My treatment needs to be delivered through the brain's ventricles due to tumor location.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of HSV-1 (G207) infused through catheters into the tumor, followed by a 5 Gy dose of radiation within 24 hours for subsequent cohorts

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety, virologic shedding, immune response, and overall survival

60 months

Regular intervals (in-person and virtual)

Treatment Details

Interventions

• G207

Trial Overview The study tests the safety of G207, an experimental virus therapy injected into recurrent or refractory cerebellar brain tumors. It also examines the effects when combined with low-dose radiation intended to boost virus replication and strengthen immune response against tumor cells.

Participant Groups

Group I: HSV G207 Experimental Treatment 1 Intervention

Single dose of HSV-1 (G207) infused through catheters into region(s) of tumor. If G207 is safe in the first cohort of patients, subsequent patients will receive a single dose of G207 infused through catheters into region(s) of tumor followed by a 5 Gy dose of radiation to the tumor given with 24 hours of virus inoculation.

G207 is already approved in United States for the following indications:

Approved in United States as G207 for:

• Recurrent/progressive pediatric high-grade gliomas

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Gregory K. Friedman, MD

Lead Sponsor

Trials

2

Recruited

40+

Cannonball Kids' Cancer Foundation

Collaborator

Trials

6

Recruited

140+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

Cannonball Kids' Cancer Foundation

Collaborator

Trials

4

Recruited

110+

Treovir, Inc

Collaborator

Trials

1

Recruited

20+

Findings from Research

The G207 double mutant of herpes simplex virus type 1 shows promise for treating malignant brain tumors, specifically glioblastomas, as it can replicate in glioma cells while being safe for normal brain tissue.

In studies with nude mice, G207 significantly reduced tumor growth and improved survival rates without causing harmful effects, indicating its potential for clinical evaluation in glioblastoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. Mineta, T., Rabkin, SD., Yazaki, T., et al.[2023]

G207, a genetically engineered herpes simplex virus, shows promise as a treatment for malignant brain tumors in children, with preclinical studies indicating it can effectively target and kill various pediatric tumor types.

Safety has been established in previous studies with no dose-limiting toxicities observed in adults, and about 50% of treated adults showed signs of tumor response, suggesting potential efficacy for future pediatric applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Phase 1 Clinical Trial to Evaluate HSV G207 Alone or with a Single Radiation Dose in Children with Progressive or Recurrent Malignant Supratentorial Brain Tumors. Waters, AM., Johnston, JM., Reddy, AT., et al.[2021]

The ongoing pediatric phase 1 trial of the engineered herpes simplex virus-1 G207 shows that placing multiple intratumoral catheters for delivering the treatment is feasible and safe, with no significant perioperative complications reported in six children.

Accurate catheter placement was achieved in 21 out of 22 attempts, demonstrating the effectiveness of using advanced imaging and planning techniques, which may enhance the delivery of oncolytic virotherapy for brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Placement of Intratumoral Catheters for Continuous Infusion Delivery of Herpes Simplex Virus -1 G207 in Pediatric Malignant Supratentorial Brain Tumors. Bernstock, JD., Wright, Z., Bag, AK., et al.[2019]

G207, a genetically engineered herpes simplex virus, was found to be non-toxic when administered to the cerebellum of mice, showing no harmful effects on brain or organ health after 7 and 30 days.

The treatment with G207 significantly increased survival rates in mice with aggressive MYC-overexpressed group 3 medulloblastoma, suggesting its potential as an effective therapy for children with difficult-to-treat cerebellar tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of oncolytic HSV-1 G207 inoculated into the cerebellum of mice. Bernstock, JD., Vicario, N., Li, R., et al.[2021]

G207, a modified herpes simplex virus, has been shown to be safe for patients with recurrent malignant gliomas when administered in two doses before and after tumor resection, with no severe adverse effects reported.

Preliminary evidence suggests that G207 may have antitumor activity, as indicated by radiographic and neuropathologic findings, and it demonstrated viral replication in the treated areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. Markert, JM., Liechty, PG., Wang, W., et al.[2023]

G207, a modified herpes simplex virus, was safely administered to 21 patients with malignant gliomas, with doses escalating from 10^6 to 3x10^9 plaque forming units, and no serious adverse events linked to the treatment were observed.

The study provided early evidence of anti-tumor activity, as indicated by radiographic and neuropathologic findings, along with the long-term presence of viral DNA in some patients, suggesting potential therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Markert, JM., Medlock, MD., Rabkin, SD., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Phase 1 Clinical Trial to Evaluate HSV G207 Alone or with a Single Radiation Dose in Children with Progressive or Recurrent Malignant Supratentorial Brain Tumors. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Stereotactic Placement of Intratumoral Catheters for Continuous Infusion Delivery of Herpes Simplex Virus -1 G207 in Pediatric Malignant Supratentorial Brain Tumors. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Therapy of experimental human brain tumors using a neuroattenuated herpes simplex virus mutant. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of oncolytic HSV-1 G207 inoculated into the cerebellum of mice. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Oncolytic virus therapy using genetically engineered herpes simplex viruses. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Immuno-viral therapy as a new approach for the treatment of brain tumors. [2019]