HSV G207 Alone or With a Single Radiation Dose in Children With Progressive or Recurrent Supratentorial Brain Tumors

NCT02457845 | Completed Phase 1 DMC

• 2 other identifiers: UAB 1472R01FD005379
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a clinical trial to determine the safety of injecting G207 (a new experimental virus therapy) into a recurrent or progressive brain tumor. The safety of combining G207 with a single low dose of radiation, designed to enhance virus replication and tumor cell killing, will also be tested.

Conditions

Supratentorial Neoplasms, Malignant; Malignant Glioma; Glioblastoma; Anaplastic Astrocytoma; PNET; Cerebral Primitive Neuroectodermal Tumor; Embryonal Tumor

Keywords

Brain Tumor, Recurrent; Glioma; Glioblastoma; Gliosarcoma; Anaplastic Astrocytoma; Oligodendroglioma; Rhabdoid Tumor; Cerebral Primitive Neuroectodermal Tumor; PNET; Ependymoma; Germ Cell Tumor; Choroid Plexus Carcinoma; Oncolytic Virus Therapy; Virotherapy, Oncolytic; Immunotherapy; Central Nervous System Agents; Antineoplastic Agents; Neoplasms; Pediatric; Pediatrics; Embryonal Tumor; Oncolytic; Virus; HSV; 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 v4.0) will be tabulated by event and by relationship to G207.

  Baseline to 15 years

Secondary Outcomes (6)

• Immunologic Response

  Baseline to 12 months

• Virologic Shedding

  Baseline to 15 years

• Progression Free Survival

  Baseline to 24 months

• Overall Survival

  Baseline to 24 months

• Change in Performance (Ability to Perform Normal Activities)

  Baseline to 12 months

Study Arms (1)

HSV G207

EXPERIMENTAL

Single dose of HSV-1 (G207) infused through catheters into region(s) of tumor defined by MRI. If G207 is safe in the first two cohorts of patients, subsequent patients will receive a single dose of G207 infused through catheters into region(s) of tumor defined by MRI followed by a 5 Gy dose of radiation to the tumor given with 24 hours of virus inoculation. Intervention: Biological: G207

Biological: G207

Interventions

G207 BIOLOGICAL

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

HSV G207

Eligibility Criteria

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

You may qualify if:

• Age ≥ 36 months and \< 19 years
• Pathologically proven malignant supratentorial brain tumor (including 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 tumor without curative treatment options is eligible.
• Lesion must be \> 1.0 cm in diameter and surgically accessible as determined by MRI
• 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: 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 \> 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 \< 10 years, Modified Lansky score ≥ 60; patients \> 10 years, Karnofsky 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:

• Acute infection, granulocytopenia or medical condition precluding surgery
• Pregnant or lactating females
• Prior history of encephalitis, multiple sclerosis, or other central nervous system (CNS) infection
• Tumor involvement which would require ventricular, cerebellar or brainstem inoculation or would require access through a ventricle in order to deliver treatment
• Required steroid increase within 1 week prior to injection
• Known HIV seropositivity
• Concurrent therapy with any drug active against HSV (acyclovir, valaciclovir, penciclovir, famciclovir, gancyclovir, foscarnet, cidofovir) or any immunosuppressive drug therapy (except dexamethasone or prednisone).

Sponsors & Collaborators

• Gregory K. Friedman, MD: lead
• Food and Drug Administration (FDA): collaborator
• National Center for Advancing Translational Sciences of the National Institutes of Health: collaborator
• Cannonball Kids' Cancer Foundation: collaborator
• Rally Foundation for Childhood Cancer Research: collaborator
• Hyundai Hope On Wheels: collaborator
• St. Baldrick's Foundation: collaborator
• United States Department of Defense: collaborator
• The Andrew McDonough B+ Foundation: collaborator
• Kaul Pediatric Research Institute: collaborator
• University of Alabama at Birmingham: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• Kelsie's Crew: collaborator
• Eli's Block Party Childhood Cancer Foundation: collaborator
• Eli Jackson Foundation: collaborator
• Jaxon's F.R.O.G. Foundation: collaborator
• Battle for a Cure Foundation: collaborator
• Sandcastle Kids: collaborator

Study Sites (2)

Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (1)

• Friedman GK, Johnston JM, Bag AK, Bernstock JD, Li R, Aban I, Kachurak K, Nan L, Kang KD, Totsch S, Schlappi C, Martin AM, Pastakia D, McNall-Knapp R, Farouk Sait S, Khakoo Y, Karajannis MA, Woodling K, Palmer JD, Osorio DS, Leonard J, Abdelbaki MS, Madan-Swain A, Atkinson TP, Whitley RJ, Fiveash JB, Markert JM, Gillespie GY. Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas. N Engl J Med. 2021 Apr 29;384(17):1613-1622. doi: 10.1056/NEJMoa2024947. Epub 2021 Apr 10.

  PMID: 33838625 DERIVED

Related Links

• Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas

MeSH Terms

Conditions

Supratentorial Neoplasms; Glioma; Glioblastoma; Astrocytoma; Neuroectodermal Tumors, Primitive; Neoplasms, Germ Cell and Embryonal; Brain Neoplasms; Gliosarcoma; Oligodendroglioma; Rhabdoid Tumor; Ependymoma; Choroid Plexus Carcinoma; Neoplasms; Virus Diseases

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Infections

Study Officials

• Gregory K Friedman, M.D.

  University of Alabama at Birmingham (UAB)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 20, 2015
• First Posted: May 29, 2015
• Study Start: May 1, 2016
• Primary Completion: June 1, 2020
• Study Completion: January 1, 2024
• Last Updated: January 19, 2024

Record last verified: 2024-01

Locations

US (2)