HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors
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|ClinicalTrials.gov Identifier: NCT03911388|
Recruitment Status : Recruiting
First Posted : April 11, 2019
Last Update Posted : September 17, 2019
|Condition or disease||Intervention/treatment||Phase|
|Neoplasms, Brain Glioblastoma Multiforme Glioblastoma of Cerebellum Neoplasms Astrocytoma Astrocytoma, Cerebellar Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Cerebellar PNET, Childhood Cerebellar Neoplasms Cerebellar Neoplasms, Primary Cerebellar Neoplasm, Malignant Cerebellar Neoplasm Malignant Primary Neoplasm Metastases Neoplasm Malignant Neoplasms, Neuroepithelial Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Central Nervous System Neoplasms, Primary Central Nervous System Neoplasms, Malignant Nervous System Neoplasms Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases Medulloblastoma Recurrent HSV Virus Pediatric Brain Tumor Nervous System Cancer Primitive Neuroectodermal Tumor (PNET) of Cerebellum||Biological: G207||Phase 1|
Outcomes for children with recurrent or progressive cerebellar 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 safety of G207 has been demonstrated in 3 phase I clinical trials involving adults with supratentorial high-grade gliomas adults at the University of Alabama (UAB) and in an ongoing phase I clinical trial involving children with recurrent supratentorial brain tumors at Children's of Alabama. In the adult 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 anti-tumor responses have been seen. 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 cerebellar 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 cohort will receive G207 alone, and the next cohorts will receive G207 at one of three doses followed by a 5 Gy dose of radiation to active areas of tumor.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||A traditional 3 + 3 design will be used with four patient cohorts.|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Trial of Engineered HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors|
|Actual Study Start Date :||September 12, 2019|
|Estimated Primary Completion Date :||September 1, 2022|
|Estimated Study Completion Date :||September 1, 2023|
Experimental: HSV G207
Single dose of HSV-1 (G207) infused through catheters into region(s) of tumor. If G207 is safe in the first cohort of patients, subsequent patients will receive a single dose of G207 infused through catheters into region(s) of tumor followed by a 5 Gy dose of radiation to the tumor given with 24 hours of virus inoculation.
Single dose of G207 infused through catheters into region(s) of tumor. If G207 is safe in the first cohort of patients, subsequent patients will receive a single dose of G207 infused through catheters into region(s) of tumor followed by a 5 Gy dose of radiation to the tumor (which includes progressive leptomeningeal disease or any site of gross tumor progressing in the brain parenchyma) within 24 hours of virus inoculation.
Other Name: HSV G207
- 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 v5.0) will be tabulated by event and by relationship to G207.
- Immunologic Response [ Time Frame: Baseline to 24 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 ]HSV-1 antibody titers will be checked by ELISA prior to the administration of G207 and at regular intervals after treatment.
- 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 60 months ]The overall survival for each patient receiving G207 will be calculated
- Change in Performance (Ability to Perform Normal Activities) [ Time Frame: Baseline to 24 months ]A modified Lansky score (for children under 16 years of age) or Karnofsky score (for children 16 and older) will be recorded pre-treatment and measured serially at regular intervals after treatment. The score is a standard performance score that measures overall function of the child with a scale range from 0 (lowest, poorest performance score) to 100 (highest, best performance).
- Quality of Life (optional) [ Time Frame: Baseline to 24 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): NCT03911388
|Contact: Gregory Friedman, MD||(205) email@example.com|
|Contact: Kara Kachurack, CRNP||(205) firstname.lastname@example.org|
|United States, Alabama|
|Children's of Alabama||Recruiting|
|Birmingham, Alabama, United States, 35233|
|Contact: Kara Kachurak, CRNP 205-638-9285 email@example.com|
|Contact: Gregory Friedman, MD (205) 638-9285 firstname.lastname@example.org|
|Principal Investigator:||Gregory Friedman, MD||University of Alabama at Birmingham|