HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors

NCT03911388 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 2023-0688R01FD006368NCI-2021-00011
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

This study is a clinical trial to determine the safety of inoculating G207 (an experimental virus therapy) into a recurrent or refractory cerebellar brain tumor. The safety of combining G207 with a single low dose of radiation, designed to enhance virus replication, tumor cell killing, and an anti-tumor immune response, will also be tested. Funding Source- FDA OOPD

Conditions

Neoplasms by Histologic Type; Neoplasms by Site; Brain Diseases; HSV; Pediatric Brain Tumor; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms, Primary; Central Nervous System Diseases; Nervous System Diseases; Medulloblastoma Recurrent; Neoplasms, Brain; Glioblastoma Multiforme; Glioblastoma of Cerebellum; Neoplasms; Astrocytoma; Astrocytoma, Cerebellar; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Cerebellar PNET, Childhood; Cerebellar Neoplasms; Cerebellar Neoplasms, Primary; Cerebellar Neoplasm, Malignant; Cerebellar Neoplasm Malignant Primary; Neoplasm Metastases; Neoplasm Malignant; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Central Nervous System Neoplasms, Malignant; Nervous System Neoplasms; Virus; Nervous System Cancer; Primitive Neuroectodermal Tumor (PNET) of Cerebellum

Keywords

Brain Tumor, Recurrent; Glioma; Glioblastoma Multiforme; Gliosarcoma; Medulloblastoma; Anaplastic Astrocytoma; Oligodendroglioma; Rhabdoid Tumor; Ependymoma; Germ Cell Tumor; Choroid Plexus Carcinoma; Cerebral Primitive Neuroectodermal Tumor; Giant Cell Glioblastoma; Atypical teratoid/rhabdoid tumor; Secondary Malignant Cerebellar Tumor; Embryonal Tumor; Neoplasms; Oncolytic Virus Therapy; Virotherapy, Oncolytic; Immunotherapy; Central Nervous System Agents; Antineoplastic Agents; Pediatric; Pediatrics; Oncolytic; Virus; HSV; Herpes Virus; G207; Oncolytic Herpes Virus

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability as Measured by Frequency of Grade 3 or Above Adverse Events

  All events with a Grade 3 or above toxicity (defined by the CTCAE v5.0) will be tabulated by event and by relationship to G207.

  Baseline to 15 years

Secondary Outcomes (6)

• Immunologic Response

  Baseline to 24 months

• Virologic Shedding

  Baseline to 15 years

• Progression Free Survival

  Baseline to 24 months

• Overall Survival

  Baseline to 60 months

• Change in Performance (Ability to Perform Normal Activities)

  Baseline to 24 months

Study Arms (1)

HSV G207

EXPERIMENTAL

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.

Biological: G207

Interventions

G207 BIOLOGICAL

Single dose of 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 (which includes progressive leptomeningeal disease or any site of gross tumor progressing in the brain parenchyma) within 24 hours of virus inoculation.

Also known as: HSV G207

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:

• Age ≥ 36 months and \< 22 years
• Pathologically proven malignant cerebellar brain tumor (including medulloblastoma, glioblastoma multiforme, giant cell glioblastoma, anaplastic astrocytoma, primitive neuroectodermal tumor, ependymoma, atypical teratoid/rhabdoid tumor, germ cell tumor, or other high-grade malignant tumor) which is progressive or recurrent despite standard care including surgery, radiotherapy, and/or chemotherapy. A pathologically proven secondary malignant cerebellar tumor without curative treatment options is eligible.
• Lesion must be ≥ 1.0 cm ≤ 3.0 cm in diameter and surgically accessible as determined by MRI. Larger tumors may be surgically debulked and treated if ≤ 3.0 cm after debulking
• Patients must have fully recovered from acute treatment related toxicities of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study.
• Myelosuppressive chemotherapy: patients must have received their last dose at least 3 weeks prior (or at least 6 weeks if nitrosurea)
• Investigational/Biologic agents: patients must have recovered from any acute toxicities potentially related to the agent and received last dose ≥ 7 days prior to entering this study (this period must be extended beyond the time during which adverse events are known to occur for agents with known adverse events ≥ 7 days). For viral therapy, patients must have received viral therapy ≥ 3 months prior to study entry and have recovered from all acute toxicities potentially related to the agent.
• Monoclonal antibodies: The patient must have received last dose ≥ 21 days prior.
• Radiation: Patients must have received their last fraction of craniospinal radiation (\>24 Gy) or total body irradiation ≥ 3 months prior to study entry. Patients must have received focal radiation to symptomatic metastatic sites or local palliative radiation ≥ 28 days prior to study entry.
• Autologous bone marrow transplant: Patients must be ≥ 3 months since transplant prior to study entry.
• Normal hematological, renal and liver function (absolute neutrophil count \> 1000/mm3, platelets \> 100,000/mm3, prothrombin time (PT) or partial thromboplastin time (PTT) \< 1.3 x control, creatinine within normal institutional limits OR creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, total bilirubin \< 1.5 mg/dl, transaminases \< 3 times above the upper limits of the institutional norm)
• Patients \< 16 years, Modified Lansky performance score ≥ 60; patients ≥ 16 years, Karnofsky performance score ≥ 60
• Patient life expectancy must be at least 8 weeks
• Written informed consent in accordance with institutional and FDA guidelines must be obtained from patient or legal guardian

You may not qualify if:

• Any treatment outside the allowable guidelines outlined in section 5.1.
• Diffuse, widespread, abnormal tumor pattern involving 3 or more lobes of the brain
• Acute infection, granulocytopenia or medical condition precluding surgery
• Pregnant or lactating females
• Diagnosis of encephalitis or CNS infection \< 3 months prior, or receiving ongoing treatment for encephalitis, CNS infection or multiple sclerosis
• Tumor involvement which would require ventricular or brainstem inoculation or would require access through a ventricle in order to deliver treatment
• Required steroid increase within 1 week prior to G207 inoculation or patients requiring \>2 mg of dexamethasone daily
• Known HIV seropositivity
• Concurrent therapy with any drug active against HSV (acyclovir, valacyclovir, penciclovir, famciclovir, gancyclovir, foscarnet, cidofovir) or any immunosuppressive drug therapy (except dexamethasone or prednisone).
• Other current malignancy
• Concurrent anticancer or investigational drug

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Cannonball Kids' Cancer Foundation: collaborator
• Treovir, Inc: collaborator

Study Sites (3)

Children's of Alabama

Birmingham, Alabama, 35233, United States

ACTIVE NOT RECRUITING

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

ACTIVE NOT RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Brain Neoplasms; Glioblastoma; Neoplasms; Astrocytoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Medulloblastoma; Cerebellar Neoplasms; Neoplasm Metastasis; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Glioma; Gliosarcoma; Oligodendroglioma; Rhabdoid Tumor; Ependymoma; Choroid Plexus Carcinoma

Condition Hierarchy (Ancestors)

Infratentorial Neoplasms; Cerebellar Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Neoplasms, Complex and Mixed

Study Officials

• Gregory Friedman, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kara Kachurak, CRNP

CONTACT

832-750-5661l; kgkachurak@mdanderson.org

Gregory K Friedman, MD

CONTACT

gkfriedman@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A traditional 3 + 3 design will be used with four patient cohorts.

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: April 11, 2019
• Study Start: September 12, 2019
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)