ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02457845
Recruitment Status : Recruiting
First Posted : May 29, 2015
Last Update Posted : November 26, 2018
Sponsor:
Information provided by (Responsible Party):
Gregory K. Friedman, MD, University of Alabama at Birmingham

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. Funding Source - FDA OOPD

Condition or disease Intervention/treatment Phase
Supratentorial Neoplasms, Malignant Malignant Glioma Glioblastoma Anaplastic Astrocytoma PNET Cerebral Primitive Neuroectodermal Tumor Embryonal Tumor Biological: G207 Phase 1

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. 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Clinical Trial of HSV G207 Alone or With a Single Radiation Dose in Children With Recurrent Supratentorial Brain Tumors
Study Start Date : May 2016
Estimated Primary Completion Date : May 2019


Arm Intervention/treatment
Experimental: HSV G207

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




Primary Outcome Measures :
  1. Safety and Tolerability as Measured by Frequency of Grade 3 or Above Adverse Events [ Time Frame: Baseline to 15 years ]
    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.


Secondary Outcome Measures :
  1. Immunologic Response [ Time Frame: Baseline to 12 months ]
    HSV-1 antibody titers will be checked by ELISA prior to the administration of G207 and at regular intervals after treatment.

  2. Virologic Shedding [ Time Frame: Baseline to 15 years ]
    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.

  3. Progression Free Survival [ Time Frame: Baseline to 24 months ]
    Time after G207 administration to clinical and radiographic disease progression will be evaluated.

  4. Overall Survival [ Time Frame: Baseline to 24 months ]
    The overall survival for each patient receiving G207 will be calculated.

  5. Change in Performance (Ability to Perform Normal Activities) [ Time Frame: Baseline to 12 months ]
    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.

  6. Quality of Life (optional) [ Time Frame: Baseline to 12 months ]
    Quality of life will be measured with questionnaires taken at baseline (before administration of G207) and at specified times thereafter.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   3 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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)
  • Monoclonal antibodies: At least 3 half-lives must have elapsed prior to study entry
  • 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 > 4 weeks 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

Exclusion Criteria:

  • 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
  • Prior participant in experimental viral therapy (e.g., adenovirus, retrovirus or herpes virus protocol)
  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02457845


Contacts
Contact: Gregory K Friedman, M.D. 205 638-9285 gfriedman@peds.uab.edu
Contact: Kara Kachurak, CRNP 205-638-9285 kkachurak@peds.uab.edu

Locations
United States, Alabama
Children's of Alabama Recruiting
Birmingham, Alabama, United States, 35233
Sponsors and Collaborators
University of Alabama at Birmingham

Responsible Party: Gregory K. Friedman, MD, Principal investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT02457845     History of Changes
Other Study ID Numbers: UAB 1472
R01FD005379 ( U.S. FDA Grant/Contract )
First Posted: May 29, 2015    Key Record Dates
Last Update Posted: November 26, 2018
Last Verified: November 2018

Keywords provided by Gregory K. Friedman, MD, University of Alabama at Birmingham:
Herpes Virus
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

Additional relevant MeSH terms:
Neoplasms
Glioblastoma
Glioma
Brain Neoplasms
Astrocytoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Supratentorial Neoplasms
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