G207 + Radiation for Pediatric Brain Tumor

Recruiting at 4 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

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for children with aggressive brain tumors that haven't responded to other treatments. The treatment uses a special virus injected into the tumor, followed by a small dose of radiation. The virus kills cancer cells and helps the immune system fight the tumor.

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.

What data supports the effectiveness of the treatment G207 + Radiation for Pediatric Brain Tumor?

Research shows that G207, a genetically engineered herpes simplex virus, has been effective in targeting and killing cancer cells in both adult and pediatric brain tumor models. In adult trials, about half of the patients showed a positive response, and preclinical studies in children indicate high sensitivity of various pediatric tumors to G207. ^{1 2 3 4 5}

Is the G207 treatment safe for use in humans?

G207, a genetically engineered herpes simplex virus, has been tested in several studies and shown to be safe in humans, including children and adults with brain tumors. No serious side effects directly linked to G207 were reported, and no patients developed herpes encephalitis (brain inflammation caused by the virus). ^{1 2 3 6 7}

What makes the treatment G207 unique for pediatric brain tumors?

G207 is a genetically engineered herpes simplex virus designed to specifically target and kill tumor cells without harming normal brain cells, making it a novel approach compared to traditional treatments like surgery, radiation, and chemotherapy. It is administered directly into the tumor through catheters, allowing for targeted delivery and potentially reducing side effects. ^{1 6 7 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 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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

References

1. 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]

2. United States 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Oncolytic virotherapy: Potentially a game-changing tumor treatment. [2021]

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

The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors. [2022]

6. 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]

7. United States 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. [2021]

8. 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]

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

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