RecruitingPhase 1NCT03911388

HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors

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

Sponsor

M.D. Anderson Cancer Center

Enrollment

24 participants

Start Date

Sep 12, 2019

Study Type

INTERVENTIONAL

Summary

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

Eligibility

Min Age: 3 YearsMax Age: 21 Years

Inclusion Criteria13

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.
Lesion must be ≥ 1.0 cm ≤ 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
Patients must have fully recovered from acute treatment related toxicities of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study.
Myelosuppressive chemotherapy: patients must have received their last dose at least 3 weeks prior (or at least 6 weeks if nitrosurea)
Investigational/Biologic agents: patients must have recovered from any acute toxicities potentially related to the agent and received 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, patients must have received viral therapy ≥ 3 months prior to study entry and have recovered from all acute toxicities potentially related to the agent.
Monoclonal antibodies: The patient must have received last dose ≥ 21 days prior.
Radiation: Patients must have received their last fraction of craniospinal radiation (\>24 Gy) or total body irradiation ≥ 3 months prior to study entry. Patients must have received focal radiation to symptomatic metastatic sites or local palliative radiation ≥ 28 days prior to study entry.
Autologous bone marrow transplant: Patients must be ≥ 3 months since transplant prior to study entry.
Normal hematological, renal and liver function (absolute neutrophil count \> 1000/mm3, platelets \> 100,000/mm3, 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 m2 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
Patient life expectancy must be at least 8 weeks
Written informed consent in accordance with institutional and FDA guidelines must be obtained from patient or legal guardian

Exclusion Criteria11

Any treatment outside the allowable guidelines outlined in section 5.1.
Diffuse, widespread, abnormal tumor pattern involving 3 or more lobes of the brain
Acute infection, granulocytopenia or medical condition precluding surgery
Pregnant or lactating females
Diagnosis of encephalitis or CNS infection \< 3 months prior, or 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
Required steroid increase within 1 week prior to G207 inoculation or patients requiring \>2 mg of dexamethasone daily
Known HIV seropositivity
Concurrent therapy with any drug active against HSV (acyclovir, valacyclovir, penciclovir, famciclovir, gancyclovir, foscarnet, cidofovir) or any immunosuppressive drug therapy (except dexamethasone or prednisone).
Other current malignancy
Concurrent anticancer or investigational drug

Interventions

BIOLOGICALG207

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.