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Supratentorial Neoplasms, MalignantPhase 1NCT02457845

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

A Phase 1 study testing G207 in people with Supratentorial Neoplasms, Malignant and Malignant Glioma, run by Gregory K. Friedman, MD at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 3 to 18 years
What is being tested?
G207
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
2 sitesUnited States
Study dates
May 2016to Jan 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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).

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Children's of Alabama

    Birmingham, Alabama, 35233

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

Other trials in United States

About this study

Official title: Phase I Clinical Trial of HSV G207 Alone or With a Single Radiation Dose in Children With Recurrent Supratentorial Brain Tumors

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.

Read the detailed description

Outcomes for children with recurrent or progressive supratentorial malignant brain tumors are very poor, and there are a lack of effective salvage therapies once a patient fails standard treatments.

G207 is an oncolytic herpes simplex virus-1 (HSV) that has been successfully engineered to introduce mutations in the virus that enable it to selectively replicate in and kill cancer cells, but not normal cells. Replication of G207 in the tumor not only kills the infected tumor cells, but causes the tumor cell to act as a factory to produce new virus. These virus particles are released as the tumor cell dies, and can then proceed to infect other tumor cells in the vicinity, and continue the process of tumor kill. In addition to this direct oncolytic activity, the virus engenders an anti-tumor immune response; the virus is immunogenic and produces a debris field which exposes cancer cell antigens to immune cells which can target other cancer cells. Thus, the oncolytic effect of the virus and the immune response that the virus stimulates provide a one-two punch at attacking cancer cells. In preclinical studies, a single 5 Gy dose of radiation within 24 hours of virus inoculation to the tumor increased virus replication and tumor cell killing.

The University of Alabama at Birmingham has conducted three phase I trials of G207 injected into the recurrent tumor alone or combined with a single dose of radiation in adults with recurrent high-grade gliomas. In these trials, high doses (up to 3 x 10^9 plaque-forming units) of virus were safely injected directly into the tumor or surrounding brain tissue without serious toxicities. A maximum tolerated dose was not reached in all 3 trials. Radiographic and neuropathologic evidence of an antitumor response was seen in some patients. Preclinical laboratory studies have demonstrated that a variety of aggressive pediatric brain tumor types are sensitive to G207.

This study is a phase I, open-label, single institution clinical trial of G207 alone or combined with a single low dose of radiation in children with recurrent or progressive supratentorial brain tumors. The primary goal is to determine safety. The secondary aims are to obtain preliminary information on the effectiveness of and immune response to G207.

A traditional 3 + 3 design will be used with four patient cohorts. The first two cohorts will receive G207 at one of two doses, and the second two cohorts will receive G207 at one of two doses followed by a 5 Gy dose of radiation.

Being tested
G207
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
Medical subject headings
Supratentorial Neoplasms, Glioma, Glioblastoma, Astrocytoma, Neuroectodermal Tumors, Primitive, Neoplasms, Germ Cell and Embryonal, Brain Neoplasms, Gliosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • G207Biological

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

Study groups in NCT02457845
Study groupRoleWhat they receive
HSV G207ExperimentalSingle 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
Receives: Biological: G207

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to 15 years

Secondary outcomes (6)

  1. Immunologic Response

    HSV-1 antibody titers will be checked by ELISA prior to the administration of G207 and at regular intervals after treatment.

    Measured: Baseline to 12 months

  2. Virologic Shedding

    Saliva, blood and conjunctival secretions will be checked by polymerase chain reaction (PCR) and culture at regular intervals for evidence of HSV shedding and/or viremia.

    Measured: Baseline to 15 years

  3. Progression Free Survival

    Time after G207 administration to clinical and radiographic disease progression will be evaluated.

    Measured: Baseline to 24 months

  4. Overall Survival

    The overall survival for each patient receiving G207 will be calculated.

    Measured: Baseline to 24 months

  5. Change in Performance (Ability to Perform Normal Activities)

    A modified Lansky score (for children under 16 years of age) or Karnofsky score (for children 16 and older) will be recorded and measured serially with the pre-treatment score.

    Measured: Baseline to 12 months

  6. Quality of Life (optional)

    Quality of life will be measured with questionnaires taken at baseline (before administration of G207) and at specified times thereafter.

    Measured: Baseline to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 May 2015 (estimated)
  2. Study startMay 2016
  3. Primary completionJun 2020
  4. Study completionJan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02457845
Sponsor's protocol ID
UAB 1472
Other IDs
R01FD005379
Status last verified
Jan 2024
First submitted
20 May 2015
Last updated
19 Jan 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 33838625

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing G207 in people with Supratentorial Neoplasms, Malignant and Malignant Glioma, run by Gregory K. Friedman, MD at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability as Measured by Frequency of Grade 3 or Above Adverse Events (time frame: Baseline to 15 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02457845, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2024.

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