G207 for Brain Cancer

Recruiting at 3 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new virus therapy, G207, to determine its safety for treating cerebellar brain tumors that have recurred or resisted standard treatments. The study will also evaluate whether a low dose of radiation enhances the virus's ability to kill tumor cells and boost the body’s immune response. The trial seeks participants with a recurrent or stubborn malignant cerebellar brain tumor, unresponsive to surgery, chemotherapy, or radiation, and measuring between 1 and 3 cm. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that G207, a specially modified herpes virus, was well-tolerated in past studies with patients who have recurring malignant brain tumors. In these studies, G207 safely targeted tumor cells without harming normal brain cells. This is encouraging because the treatment aims to kill tumor cells specifically. Tests on animals also support its safety, reinforcing these findings.

The current trial remains in the early stages, so detailed human safety data is still being collected. However, earlier research in similar situations suggests that G207 can be used safely. Additionally, researchers are investigating whether combining G207 with a small amount of radiation can enhance the treatment's effectiveness without compromising its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about G207 for brain cancer because it uses a groundbreaking approach by leveraging a genetically modified virus, HSV-1, to attack tumor cells directly. Unlike traditional treatments like surgery, chemotherapy, or radiation alone, G207 is infused directly into the tumor and, if deemed safe, is followed by a precise dose of radiation. This method not only targets cancer cells more directly but also aims to enhance the immune system's response against the tumor, potentially offering a unique and powerful option for patients.

What evidence suggests that G207 might be an effective treatment for brain cancer?

Research shows that G207, a modified form of the herpes virus, might help treat brain tumors. In earlier studies, doctors safely injected G207 into the brains of patients with malignant glioma, a type of brain cancer. The virus targets and kills cancer cells while sparing healthy cells. In this trial, participants will receive a single dose of G207 infused through catheters into the tumor region. If G207 proves safe in the first cohort of patients, subsequent participants will receive G207 followed by a 5 Gy dose of radiation within 24 hours, potentially enhancing the virus's ability to attack the tumor. Although still experimental, G207 could offer hope when other treatments have not worked. ^{1 2 3 4 6}

Who Is on the Research Team?

Gregory Friedman, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4015243/

A Phase 1 Trial of Oncolytic HSV-1, G207, Given in ... G207, a mutant herpes simplex virus (HSV) type 1, is safe when inoculated into recurrent malignant glioma. We conducted a phase 1 trial of G207 to demonstrate ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00036699

Safety and Effectiveness Study of G207, a Tumor-Killing ... This clinical trial will study the safety and effectiveness of an engineered herpes virus, G207, administered directly into the brain of patients with ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2024947

Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric ... Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03911388

HSV G207 in Children With Recurrent or Refractory ... Outcomes for children with recurrent or progressive cerebellar malignant brain tumors are very poor, and there are a lack of effective salvage therapies once a ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S187887502402045X

Herpes Simplex Oncolytic Viral Therapy for Malignant ... The authors present a comprehensive review on the history and development of oncolytic herpes simplex viral therapies for malignant glioma

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4903272/

EPT-10: PHASE I CLINICAL TRIAL OF HSV G207 ALONE ... Outcomes for children with recurrent malignant supratentorial brain tumors are extremely poor. Novel innovative treatments are greatly needed.