Description
This study is a clinical trial to determine the safety of inoculating G207 (an experimental virus therapy) into a recurrent or refractory cerebellar brain tumor. The safety of combining G207 with a single low dose of radiation, designed to enhance virus replication, tumor cell killing, and an anti-tumor immune response, will also be tested.
Funding Source- FDA OOPD
Interventions
-
G207
(Biological)
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.
Eligibility criteria
Inclusion Criteria:
* Age ≥ 36 months and \< 22 years
* Pathologically proven malignant cerebellar brain tumor (including medulloblastoma, 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 cerebellar tumor without curative treatment options is eligible.
* A review of the MRI scan will be necessary to determine if the tumor location and size are such that the patient may be included in the study. The MRI scan must be reviewed and approved by the site neurosurgeon and/or study radiologist for enrollment. The following guidelines must be met: Lesion must be ≤ 3.0 cm in diameter and surgically accessible as determined by MRI. Larger tumors may be surgically debulked and treated if ≤ 3.0 cm after debulking. Tumor measurements should be confirmed on the Immunotherapy Response Assessment in Neuro-Oncology (iRANO) form or the institutional MRI report
* Patients must have fully recovered from acute treatment-related toxicities of all prior chemotherapy, immunotherapy or radiotherapy prior to the date of G207 administration. All washout intervals below are measured relative to the date of G207 administration.
* Myelosuppressive chemotherapy: patients must have received their last dose at least 3 weeks prior (or at least 6 weeks if nitrosurea) to G207 administration.
* Monoclonal antibodies: patient must have received the last dose ≥ 21 days prior to G207 administration
* Investigational/Biologic agents: patients must have recovered from any acute toxicities potentially related to the agent and received last dose ≥ 7 days prior to G207 administration (this period must be extended beyond the time during which adverse events are known to occur for agents with known adverse events ≥\>= 7 days).
* Viral therapy: Patients must have received viral therapy ≥ 3 months prior to G207 administration and must have recovered from all acute toxicities potentially related to the agent
* Radiation: Patients must have received their last fraction of craniospinal radiation (\>24 Gy) or total body irradiation ≥ 3 months prior to G207 administration. Patients must have received focal radiation to symptomatic metastatic sites or local palliative radiation ≥ 28 days prior to G207 administration.
* Autologous bone marrow transplant: Patients must be ≥ 3 months since transplant prior to G207 administration.
* Absolute neutrophil count \> 1000/mm3
* Platelets ≥ 100,000/mm\^3
* Prothrombin time (PT) or partial thromboplastin time (PTT) ≤ 1.3 x control
* Creatinine within normal institutional limits OR creatinine clearance \>60 mL/min/1.73 m\^2 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 \< 16 years, Modified Lansky performance score ≥ 60; patients ≥ 16 years, Karnofsky performance score ≥ 60
* Written informed consent in accordance with institutional and Food and Drug Administration (FDA) guidelines must be obtained from patient or legal guardian
Exclusion Criteria:
* Acute infection, granulocytopenia or medical condition precluding surgery
* Pregnant or lactating females
* Diagnosis of encephalitis or central nervous system (CNS) infection ≤ 3 months prior
* Receiving ongoing treatment for encephalitis, CNS infection or multiple sclerosis
* Tumor involvement which would require ventricular or brainstem inoculation or would require access through a ventricle in order to deliver treatment
* Patient requires an escalation in ongoing systemic corticosteroid therapy within 7 days prior to G207 inoculation or requires ongoing systemic corticosteroid therapy at a dose \> 2 mg/day of dexamethasone (or equivalent) at the time of inoculation. For this study, 'systemic corticosteroids' include oral, intravenous, or intramuscular formulations. A single, non-consecutive dose does not constitute exclusion. Physiologic corticosteroid replacement therapy (e.g., hydrocortisone for adrenal insufficiency) is not considered immunosuppressive and does not constitute exclusion
* Known human immunodeficiency virus (HIV) seropositivity
* Concurrent therapy with any drug active against herpes simplex virus (HSV) (acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir) or any immunosuppressive drug therapy (except dexamethasone or prednisone)
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen for this trial
* Concurrent anticancer or investigational drug
Conditions
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
Locations
- University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States
- Siteman Cancer Center at Washington University — St Louis, Missouri, United States
- MD Anderson Cancer Center — Houston, Texas, United States