HSV G207 With a Single Radiation Dose in Children With Recurrent High-Grade Glioma
Neoplasms, High Grade Glioma, Glioblastoma Multiforme
About this trial
This is an interventional treatment trial for Neoplasms focused on measuring Brain Tumor, Recurrent, glioma, oncolytic virotherapy, immunotherapy, immunovirotherapy, neoplasm, progressive, virus, HSV, herpes virus, herpes simplex virus, oncolytic virus
Eligibility Criteria
Inclusion Criteria:
Patients meeting the following inclusion criteria will be eligible for the study:
- Age ≥ 3 years of age and ≤ 21 years of age at the time of study enrollment
- Patients must have a pathologically proven malignant high-grade glioma (including glioblastoma multiforme, giant cell glioblastoma, anaplastic astrocytoma, midline diffuse glioma) which is progressive or recurrent despite standard care including surgery, radiotherapy, and/or chemotherapy
- Lesion must be ≥ 1.0 cm and ≤ 4.0 cm in longest dimension and surgically accessible as determined by MRI. Larger tumors may be surgically debulked and treated if ≤ 4.0 cm after debulking
- Multifocal disease on the unilateral side is eligible if at least one catheter can be placed in all multifocal areas
- Performance score ≥ 60% (Karnofsky for children ≥16 years old; modified Lansky for children < 16 years old)
- Patients with neurological deficits should have deficits that are stable for ≥ 1 week prior to enrollment. A baseline detailed neurological exam should clearly document the neurological status of the patient at the time of enrollment on the study
- Prior therapy: patients must have recovered from acute treatment related toxicities of all prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy, biologic therapy, or virotherapy prior to entering this study
- Myelosuppressive chemotherapy: patients must have received their last dose at least 3 weeks prior and demonstrated count recovery as defined below
- Investigational/Biologic agents: patients must have recovered from any acute toxicities potentially related to the agent and received the 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 or cellular therapy, patients must have received therapy ≥ 3 months prior to study entry and have recovered from all acute toxicities potentially related to the agent.
- Monoclonal antibodies: patient must have received last dose ≥ 28 days prior
- Radiation: Patients must have received their last fraction of radiation (≥ 54 Gy) ≥ 3 months prior to study entry. Patients must have received local palliative radiation ≥ 28 days prior to study entry
- Patient must have adequate organ and marrow function as defined by the following: Hemoglobin ≥8 g/dL (may receive blood transfusions); absolute neutrophil count ≥ 1.0 x 10^9 cells/L; platelet count ≥ 100 x 10^9 cells/L (transfusion independent defined as not receiving platelets transfusions ≥ 7 days prior to enrollment); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the institutional upper limit of normal for age; creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Written informed consent in accordance with institutional and FDA guidelines must be obtained from patient or legal guardian
Exclusion Criteria:
Patients with the following conditions will be excluded from participation in the study:
- Primary cerebellar, brainstem or spinal tumors
- Metastatic disease or gliomatosis cerebri
- Acute infection or medical condition precluding surgery
- Pregnant or lactating
- Diagnosis of encephalitis or central nervous system (CNS) infection < 3 months prior, or receiving ongoing treatment for encephalitis, CNS infection or multiple sclerosis
- 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 G207 inoculation or patients requiring >4 mg of dexamethasone daily
- Known HIV seropositivity
- Concurrent therapy with any drug active against HSV (acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir) or any immunosuppressive drug therapy (except dexamethasone or prednisone).
- Other current malignancy
- Concurrent anticancer or investigational drug
Sites / Locations
- Children's of Alabama
Arms of the Study
Arm 1
Experimental
Experimental: HSV G207
All subjects will receive G207 at 1 x 10^8 plaque-forming units (pfu), intratumorally via controlled rate infusion through up to 4 silastic catheters over a 6 hour period. The subject will then receive a single 5 Gy dose of radiation to the tumor within 24 hours of virus inoculation.