HSV G207 Alone or With a Single Radiation Dose in Children With Progressive or Recurrent Supratentorial Brain Tumors
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|ClinicalTrials.gov Identifier: NCT02457845|
Recruitment Status : Recruiting
First Posted : May 29, 2015
Last Update Posted : November 26, 2018
|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|
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)|
|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|
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
Single dose of HSV-1 (G207) infused through catheters into region(s) of tumor defined by MRI
- 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.
- 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.
- 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.
- Progression Free Survival [ Time Frame: Baseline to 24 months ]Time after G207 administration to clinical and radiographic disease progression will be evaluated.
- Overall Survival [ Time Frame: Baseline to 24 months ]The overall survival for each patient receiving G207 will be calculated.
- 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.
- 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.
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
|Contact: Gregory K Friedman, M.D.||205 firstname.lastname@example.org|
|Contact: Kara Kachurak, CRNPemail@example.com|
|United States, Alabama|
|Children's of Alabama||Recruiting|
|Birmingham, Alabama, United States, 35233|