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.
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
- Conditions the study is for
- Supratentorial Neoplasms, Malignant, Malignant Glioma, Glioblastoma
- 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
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
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- 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
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.
- Conditions
- Supratentorial Neoplasms, Malignant, Malignant Glioma, Glioblastoma, Anaplastic Astrocytoma, PNET, Cerebral Primitive Neuroectodermal Tumor
- 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 group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: G207 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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
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
Progression Free Survival
Time after G207 administration to clinical and radiographic disease progression will be evaluated.
Measured: Baseline to 24 months
Overall Survival
The overall survival for each patient receiving G207 will be calculated.
Measured: Baseline to 24 months
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
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.
- First posted29 May 2015 (estimated)
- Study startMay 2016
- Primary completionJun 2020
- Study completionJan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Supratentorial Neoplasms, MalignantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Gregory K. Friedman, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Drug Administration (FDA), National Center for Advancing Translational Sciences (NCATS), Cannonball Kids' Cancer Foundation, Rally Foundation for Childhood Cancer Research, Hyundai Hope On Wheels, St. Baldrick's Foundation, United States Department of Defense, The Andrew McDonough B+ Foundation, Kaul Pediatric Research Institute, University of Alabama at Birmingham, Memorial Sloan Kettering Cancer Center, Kelsie's Crew, Eli's Block Party Childhood Cancer Foundation, Eli Jackson Foundation, Jaxon's F.R.O.G. Foundation, Battle for a Cure Foundation, Sandcastle Kids
- Responsible party
- Sponsor-investigator, Gregory K. Friedman, MD, University of Alabama at Birmingham
- Investigators
- Gregory K Friedman, M.D., Principal investigator, University of Alabama at Birmingham (UAB)
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