Phase 1 Trial of Engineered HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors

Trial ID: NCT03911388

Interventional - Phase 1 - Recruiting

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

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

Interventions

• G207

Eligibility

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

Sponsor

M.D. Anderson Cancer Center, Cannonball Kids' Cancer Foundation, Treovir, Inc

Source: ClinicalTrials.gov

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