HSV G207 With a Single Radiation Dose in Children With Recurrent High-Grade Glioma

NCT04482933 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: PBTC-061UM1CA081457NCI-2023-06938
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

Brief Summary

This study is a clinical trial to assess the efficacy and confirm the safety of intratumoral inoculation of G207 (an experimental virus therapy) combined with a single 5 Gy dose of radiation in recurrent/progressive pediatric high-grade gliomas

Conditions

Neoplasms; High Grade Glioma; Glioblastoma Multiforme; Malignant Glioma of Brain; Anaplastic Astrocytoma of Brain; High-grade Glioma; Anaplastic Glioma; Giant Cell Glioblastoma

Keywords

Brain Tumor, Recurrent; glioma; oncolytic virotherapy; immunotherapy; immunovirotherapy; neoplasm; progressive; virus; HSV; herpes virus; herpes simplex virus; oncolytic virus

Outcome Measures

Primary Outcomes (1)

• Efficacy (overall survival)

  To determine efficacy, post progression overall survival (pPD-OS) curve for patients that receive G207 will be compared to historical controls at initial recurrence. Because this is an adjuvant immunovirotherapy that can (a) result in central clearing of a tumor due to cell death and necrosis where virus is infused; (b) elicit a striking immune cell infiltration that creates a pseudoprogression 'phenotype' and (c) produce a delayed anti-tumor response, there is not an adequate response assessment tool to accurately determine an objective response rate or true progression for declaration of progression-free survival. For these reasons, we will compare post-progression overall survival observed on this study to similarly defined outcomes in historical controls.

  Baseline to 24 months

Secondary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Baseline to 5 years

• Virologic Shedding

  Baseline to 24 months

Other Outcomes (5)

• Immunologic Response: HSV-1 Antibody Titers

  Baseline to 12 months

• Immunologic Response: Expression Levels of Peripheral Blood Immune Cells, Cytokines, and Chemokines

  Baseline to 12 months

• Correlate Radiographic Changes to G207 + 5 Gy Radiation

  Baseline to 24 months

Study Arms (1)

Experimental: HSV G207

EXPERIMENTAL

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.

Biological: Biological G207

Interventions

Biological G207 BIOLOGICAL

Single dose of HSV-1 (G207) infused through catheters into region(s) of tumor defined by MRI

Also known as: Experimental: HSV G207

Experimental: HSV G207

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must have a histologically confirmed diagnosis of high-grade glioma regardless of molecular characterization that is recurrent or progressive. All tumors must have histologic verification at either the time of diagnosis or recurrence.
• Patients are only eligible after their first progression following prior surgery and radiotherapy
• Supratentorial lesion must be ≥ 1.0 cm in longest dimension and surgically accessible as determined by contrast-enhanced MRI
• For patients with tumors \> 4.0 cm without an adjacent cavity, the neurosurgeon must be confident that the tumor can be debulked to ≤ 4.0 cm for eligibility.
• Multifocal disease on the ipsilateral side is eligible if at least one catheter can be placed in all multifocal areas
• Tumor size will be determined using the maximal 2-dimensional cross-sectional tumor measurements, transverse x width, using either T1 images or T2/FLAIR images for non-enhancing tumors.
• Patient must be ≥ 3 at initial diagnosis but \< 22 years of age at the time of enrollment on this study.
• Prior therapy: Patients must have received prior surgery and radiotherapy and recovered from the acute treatment related toxicities (defined as ≤ Grade 1 if not defined in eligibility criteria; excludes alopecia) prior to enrollment.
• Chemotherapy: Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.
• Biologic or investigational agents (anti-neoplastic): patients must have received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
• Monoclonal antibodies and agents with known prolonged half-lives: Patient must have received their last dose of the agent ≥ 28 days prior to study enrollment.
• Immune Effector Cell (IEC) Therapy (e.g., CAR T cells): For viral therapy or cellular therapy, patients must have received therapy ≥ 3 months prior to study enrollment.
• Radiation: Patients must have received their last fraction of standard radiation ≥ 3 months prior to study entry.
• Stem Cell Transplant: Patient must be:
• ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease.

You may not qualify if:

• Pregnant women are excluded from this study. Female patients of childbearing potential must have a negative serum or urine pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Pregnant women are excluded from this study because G207 is an agent with the potential for teratogenic or abortifacient effects.
• Lactating females are not eligible unless they have agreed not to breastfeed their infants. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with G207, breastfeeding should be discontinued if the mother is treated with G207.
• Concurrent Illness
• Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to undergo surgery and/or tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results.
• Known HIV seropositivity.
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen for this trial.
• Patients with a secondary high-grade glioma are ineligible.
• Patient with primary tumor involving the cerebellum, brainstem or spinal cord or that would require surgical access through a ventricle in order to deliver the prescribed protocol treatment.
• Metastatic disease or diffuse, widespread, abnormal tumor pattern involving 3 or more lobes of the brain
• Tumor with evidence of clinically significant uncal herniation or midline shift, or evidence of ventricular obstruction from tumor or tonsillar herniation
• Diagnosis of encephalitis or CNS infection \< 3 months prior, or receiving ongoing treatment for encephalitis, CNS infection, or multiple sclerosis
• Concomitant Medications
• Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible.
• Patients who are receiving ≥ 1.5 mg of dexamethasone (or ≥ 10 mg of prednisone) daily
• Concurrent therapy with any drug active against HSV (acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir)

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• Treovir, LLC: collaborator
• National Cancer Institute (NCI): collaborator
• American Lebanese Syrian Associated Charities: collaborator

Study Sites (5)

Holly Lindsay MD

Aurora, Colorado, 80045, United States

Location

Memorial Sloan Kettering

New York, New York, 14263, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neoplasms; Glioma; Glioblastoma; Brain Neoplasms; Virus Diseases; Herpes Simplex

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Herpesviridae Infections; DNA Virus Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Gregory Friedman, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Phase II Clinical Trial of HSV G207 with a Single 5 Gy Radiation Dose in Children with Recurrent High-Grade Glioma

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 23, 2020
• Study Start: September 1, 2025
• Primary Completion: December 18, 2025
• Study Completion: December 18, 2025
• Last Updated: February 10, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)