Official Title

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

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

Sponsor

Pediatric Brain Tumor Consortium

Recruitment Status

RECRUITING

Study Objective

TREATMENT

ClinicalTrials.gov ID

NCT04482933

Additional Identification number

Last Update Posted

2025-06-11

Study Completion (Actual)

2030-02-15

Study Record Versions

Contacts and Locations

facility: Holly Lindsay MD
status: ACTIVE_NOT_RECRUITING
city: Aurora
state: Colorado
zip: 80045
country: United States
geoPoint: {lat=39.72943, lon=-104.83192}

facility: Memorial Sloan Kettering
status: RECRUITING
city: New York
state: New York
zip: 14263
country: United States
contacts: [{name=Sameer Farouk Sait, MBBS, role=CONTACT, phone=212-639-2153, email=faroukss@mskcc.org}]
geoPoint: {lat=40.71427, lon=-74.00597}

facility: UPMC Children's Hospital of Pittsburgh
status: RECRUITING
city: Pittsburgh
state: Pennsylvania
zip: 15224
country: United States
contacts: [{name=James Felker, MD, role=CONTACT, phone=412-692-5962, email=james.felker@chp.edu}]
geoPoint: {lat=40.44062, lon=-79.99589}

facility: MD Anderson Cancer Center
status: RECRUITING
city: Houston
state: Texas
zip: 77030
country: United States
contacts: [{name=Gregory K Friedman, MD, role=CONTACT, phone=7137451605, email=GKFriedman@mdanderson.org}, {name=Gregory K Friedman, MD, role=PRINCIPAL_INVESTIGATOR}]
geoPoint: {lat=29.76328, lon=-95.36327}

facility: Texas Children's Hospital
status: RECRUITING
city: Houston
state: Texas
zip: 77030
country: United States
contacts: [{name=Patricia Baxter, MD, MBA, role=CONTACT, phone=8328224242, email=pabaxter@texaschildrens.org}]
geoPoint: {lat=29.76328, lon=-95.36327}

Conditions

Neoplasms

High Grade Glioma

Glioblastoma Multiforme

Malignant Glioma of Brain

Anaplastic Astrocytoma of Brain

High-grade Glioma

Anaplastic Glioma

Giant Cell Glioblastoma

TargetDisease

id: M9020
name: Glioma
asFound: Glioma
relevance: HIGH

id: M14850
name: Recurrence
relevance: LOW

id: M5209
name: Brain Neoplasms
relevance: LOW

id: M17522
name: Virus Diseases
relevance: LOW

id: M9019
name: Glioblastoma
asFound: Glioblastoma
relevance: HIGH

id: M4561
name: Astrocytoma
asFound: Anaplastic Astrocytoma
relevance: HIGH

id: M9639
name: Herpes Simplex
relevance: LOW

id: M20446
name: Neoplasms, Neuroepithelial
relevance: LOW

id: M20388
name: Neuroectodermal Tumors, Primitive
relevance: LOW

id: M19845
name: Neuroectodermal Tumors
relevance: LOW

id: M12318
name: Neoplasms, Germ Cell and Embryonal
relevance: LOW

id: M12315
name: Neoplasms by Histologic Type
relevance: LOW

id: M12320
name: Neoplasms, Glandular and Epithelial
relevance: LOW

id: M12325
name: Neoplasms, Nerve Tissue
relevance: LOW

id: T2519
name: Glioma
asFound: Glioma
relevance: HIGH

id: T2518
name: Glioblastoma
asFound: Glioblastoma
relevance: HIGH

id: T364
name: Anaplastic Astrocytoma
asFound: Anaplastic Astrocytoma
relevance: HIGH

id: T4092
name: Neuroepithelioma
relevance: LOW

ProductName

IsActiveControl

IsControlDrug

IsPlacebo

ControlDrug

-

Intervention / Treatment

type: BIOLOGICAL
name: Biological G207
description: Single dose of HSV-1 (G207) infused through catheters into region(s) of tumor defined by MRI
armGroupLabels: [Experimental: HSV G207]
otherNames: [Experimental: HSV G207]

Intervention

Study Type

INTERVENTIONAL

Phase

PHASE2

Allocation

Interventional Model

SINGLE_GROUP

Subject Blind

Arm Label

Arm Type

label: Experimental: HSV G207
type: EXPERIMENTAL
description: 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.
interventionNames: [Biological: Biological G207]

NumberOfInterventionGroups

0

GroupEnrollment

Target Number of Participant

0

InstitutionLocation

InstitutionPhoneNumber

Study Site

Location Countries

Countries of recruitment

Study Start (Actual)

2025-07-01

Arm Description

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

Inclusion and Exclusion Criteria

Treatment Inclusion Criteria: Patients meeting the following inclusion criteria will be eligible for the study: * 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. * ≥ 3 months since autologous stem cell transplant prior to enrollment. * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. A baseline detailed neurological exam should clearly document the neurological status of the patient at the time of enrollment on the study. * Patients with seizure disorders may be enrolled if seizures are well controlled. * Karnofsky Performance Scale (KPS for children \> 16 years of age) or Lansky Performance Score (LPS for children ≤ 16 years or age) assessed within 7 days prior to enrollment must be ≥ 60. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Patients must have adequate organ and marrow function as defined below: * Absolute neutrophil count \> 1.0 x 109 cells/L * Platelets \> 100 x 109 cells/L (unsupported, defined as no platelet transfusion within 7 days) * Hemoglobin ≥ 8 g/dL (may receive transfusions) * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) * PT/INR, PTT ≤ 1.5 x ULN * ALT(SGPT) and AST (SGOT) \< 3 x institutional upper limit of normal (ULN) * Albumin ≥ 3 g/dL * Serum creatinine based on age/gender as noted in Table 2. Patients that do not meet the criteria in Table 2 but have a Cystatin C, 24-hour Creatinine Clearance or GFR (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m2 are eligible. Age Maximum Serum Creatinine (mg/dL): 1 to \< 2 years: Male 0.6, Female 0.6; 2 to \< 6 years: Male 0.8, Female 0.8, 6 to \< 10 years: Male 1, Female 1; 10 to \< 13 years: Male 1.2, Female 1.2; 13 to \< 16 years: Male 1.5 Female 1.4; ≥ 16 years: Male 1.7, Female 1.4 * Corticosteroids: Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment. * Growth Factors: Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (e.g., filgrastim, sargramostim, or erythropoietin). Two (2) weeks must have elapsed if the patient received a long-acting formulation. * Pregnancy Prevention: Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study. Exclusion Criteria: 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) * Patients may not be on immunosuppressive therapy, including corticosteroids (except for patients receiving \< 1.5 mg of dexamethasone or \< 10 mg of prednisone daily) at time of enrollment. However, patients who require intermittent use of bronchodilators or topical steroids will not be excluded from the study. 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. Prior Cranial Spinal Irradiation: Patients who received cranial spinal irradiation (CSI) are ineligible.

minimum age

3 Years

maximum age

21 Years

Standard ages

CHILD

ADULT

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

NO

Enrollment (Actual)

35

Original Enrollment (Actual)

0

Final Enrollment Number

0

FinalSubjectSelectionDate

AnalysisTargetGroup

DemographicInformation

Primary Outcome Measures

measure: Efficacy (overall survival)
description: 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.
timeFrame: Baseline to 24 months

Secondary Outcome Measures

measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
description: Safety/tolerability will be assessed by adverse events and laboratory tests. Adverse events will be described and the frequency of events will be tabulated. All events within the first 30 days of G207 administration will be summarized separately and tabulated by event, grade, and by relationship to G207. In addition, any Grade 3 or above toxicity (where toxicity is defined by the CTCAE v5.0) will be summarized separately and tabulated by event and by relationship to G207. Concurrent illnesses will be listed and examined as possible confounders in the treatment response relationship. Concurrent medications will also be listed, as will previous treatments for malignant brain tumors. Effects of concomitant medications and previous treatments for cancer and any potential related side effects will be analyzed and discussed.
timeFrame: Baseline to 5 years

measure: Virologic Shedding
description: Virologic shedding will be assessed from saliva, conjunctiva and blood by polymerase chain reaction (PCR)
timeFrame: Baseline to 24 months

PrimaryEndpointResult

Primary Completion Date (Actual)

2029-12-16

ClinicalTrialResultSummary

Telephone

Address

Name

Title

Telephone

name: Rachel M Chon, DNP
role: CONTACT
phone: (901) 481-5848
email: rachel.chon@stjude.org

name: Anneliese Rosdil, MSN
role: CONTACT
phone: (901) 293-1239
email: anneliese.rosdil@stjude.org

Affiliation