G207 + Radiation for Pediatric Brain Tumor

Not currently recruiting at 5 trial locations

Overseen By Gregory Friedman, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Pediatric Brain Tumor Consortium

Must not be taking: Anticancer drugs, HSV drugs

Disqualifiers: Pregnancy, HIV, Secondary glioma, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new virus therapy called G207, combined with a dose of radiation, to treat children and young adults with recurrent or worsening high-grade glioma. The goal is to determine the safety and effectiveness of this treatment. Eligible participants should have previously undergone brain surgery and radiation, and their tumors must be of a specific size and location suitable for this approach. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking any other anti-cancer or investigational drug therapy, and you cannot be on certain medications like high doses of dexamethasone or drugs active against HSV (a type of virus). If you're on immunosuppressive therapy, you may need to stop, unless it's a low dose of certain steroids.

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

Research shows that G207, a new virus-based treatment, is being tested for safety in children with brain tumors. In earlier studies, most patients tolerated G207 well. Although exact details on side effects aren't provided, the research suggests that G207 could be beneficial for this difficult-to-treat cancer. As a Phase 2 trial, the treatment has already passed initial safety checks, indicating that G207 is likely safe for further testing in children with brain tumors. However, all treatments can have risks, and joining a trial is a personal choice. It is crucial to consult healthcare providers before making a decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about G207 for pediatric brain tumors because it uses a genetically modified herpes simplex virus to directly target and destroy cancer cells. Unlike standard treatments such as surgery, chemotherapy, and traditional radiation, G207 is delivered directly into the tumor via catheters, allowing for precise targeting. Additionally, when combined with a low dose of radiation, this approach is designed to enhance the virus's cancer-fighting capabilities, potentially leading to more effective results with fewer side effects. This innovative method offers hope for a more targeted and less invasive treatment option for young patients.

What evidence suggests that G207 combined with radiation might be an effective treatment for pediatric brain tumors?

Research has shown that G207, a new virus-based treatment, may help treat high-grade brain tumors in children. In this trial, all participants will receive G207, which early results suggest attacks and destroys cancer cells. These tumors appear to respond better to the virus in children than in adults. Additionally, participants will receive a single dose of radiation, as adding radiation might enhance the treatment's effectiveness. Patients with similar conditions have shown positive responses, offering hope that G207 could be a useful treatment. While more research is needed, using a virus to fight cancer represents an exciting development. ^{4 6 7 8 9}

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 with recurrent high-grade gliomas, who've had prior surgery and radiotherapy. They must have stable neurological deficits, if any, and adequate organ/marrow function. Those on a steady or decreasing dose of dexamethasone are eligible. Patients cannot join if they have HIV, cerebellum/brainstem/spinal cord tumors requiring ventricular access, widespread brain involvement, recent CNS infections or encephalitis, ongoing anti-cancer treatments other than the study's protocol.

Inclusion Criteria

My hemoglobin level is at least 8 g/dL, transfusions are okay.

Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

PT/INR, PTT ≤ 1.5 x ULN

Exclusion Criteria

Inability to participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to drug administration plan, other study procedures, and study restrictions.

I am not taking any medication for herpes.

Pregnant women are excluded from this study. Lactating females are not eligible unless they have agreed not to breastfeed their infants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive G207 at 1 x 10^8 pfu intratumorally via controlled rate infusion through up to 4 silastic catheters over a 6-hour period, followed by a single 5 Gy dose of radiation to the tumor within 24 hours

1 week

Follow-up

Participants are monitored for safety, efficacy, and immunologic response after treatment

24 months

Long-term follow-up

Participants are monitored for long-term safety and efficacy outcomes

5 years

What Are the Treatments Tested in This Trial?

Interventions

• G207

Trial Overview The trial tests G207 (an experimental virus therapy) combined with a single radiation dose in pediatric patients with recurring brain tumors called high-grade gliomas. The aim is to see how effective this combination is at treating these tumors and confirm its safety.

How Is the Trial Designed?

Group I: Experimental: HSV G207 Experimental Treatment 1 Intervention

All subjects will receive G207 at 1 x 10\^8 plaque-forming units (pfu), intratumorally via controlled rate infusion through up to 4 silastic catheters over a 6 hour period. The subject will then receive a single 5 Gy dose of radiation to the tumor within 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?

Pediatric Brain Tumor Consortium

Lead Sponsor

Trials

38

Recruited

1,600+

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

American Lebanese Syrian Associated Charities (ALSAC)

Collaborator

Trials

9

Recruited

670+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Treovir, LLC

Collaborator

Trials

1

Recruited

40+

American Lebanese Syrian Associated Charities

Collaborator

Trials

9

Recruited

670+

Published Research Related to This Trial

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]

A Phase 1 clinical trial is being conducted to evaluate the safety and tolerability of the oncolytic herpes simplex virus G207 combined with low-dose radiation in treating recurrent malignant pediatric cerebellar tumors, which are challenging to treat and often lead to poor outcomes.

The trial aims to not only assess safety but also to gather data on the efficacy of this treatment approach by monitoring tumor response, survival rates, and quality of life, potentially paving the way for more effective and less harmful therapies for children with brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and Rationale for First-in-Human Phase 1 Immunovirotherapy Clinical Trial of Oncolytic HSV G207 to Treat Malignant Pediatric Cerebellar Brain Tumors. Bernstock, JD., Bag, AK., Fiveash, J., et al.[2021]

A phase I trial involving locally administered oncolytic herpes simplex virus-1 combined with radiation therapy demonstrated safety and feasibility for treating progressive pediatric high-grade gliomas.

Patients in the trial exhibited a surprisingly positive clinical response and showed signs of immune activation in the tissues after treatment, suggesting potential effectiveness of this combined approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic virotherapy: Potentially a game-changing tumor treatment. Kessler, T., Wick, W.[2021]

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 phase 1 trial of G207, a modified herpes simplex virus, demonstrated safety when administered intratumorally in nine patients with recurrent malignant glioma, with no cases of HSV encephalitis reported.

Patients showed potential clinical responses, with six out of nine experiencing stable disease or partial response, and a median survival time of 7.5 months following G207 treatment, suggesting promise for further research in oncolytic virus therapy for gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses. Markert, JM., Razdan, SN., Kuo, HC., et al.[2021]

Genetically engineered herpes simplex viruses, particularly the R4009 mutant, have shown promising results in treating malignant gliomas, significantly prolonging survival in a mouse model and even eradicating tumors in some cases.

The study highlights the potential of using oncolytic viruses, like R4009 and other gamma (1)34.5 mutants, as a novel therapeutic approach for primary brain tumors, demonstrating both efficacy in tumor reduction and the possibility of long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors. Andreansky, SS., He, B., Gillespie, GY., et al.[2022]

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]

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7585605/

Design and Rationale for First-in-Human Phase 1 ... Thus, based on the infratentorial propensity of pediatric brains tumors, a recent preclinical study demonstrating heightened efficacy of G207 in targeting ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04482933

NCT04482933 | HSV G207 With a Single Radiation Dose ... Outcomes for children with recurrent or progressive high-grade glioma (brain tumor) are very poor, and there are a lack of effective salvage therapies once ...

4. nature.com nature.com/articles/s41598-018-32353-x

Enhanced Sensitivity of Patient-Derived Pediatric High- ... We found that pediatric brain tumors were more sensitive to the viruses and expressed significantly more nectin-1 (CD111) than adult glioblastoma.

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/PMC8284840/

Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High ... Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months.

7. 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 ...

8. nejm.org nejm.org/doi/abs/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 5.6 months.

9. 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.