Testing a New Anti-cancer Drug, G207, Combined with Radiation in Brain Tumors that have Gotten Worse or Come Back after Treatment

Inclusion Criteria

• ELIGIBILITY CRITERIA FOR OPTIONAL SCREENING: Recurrent or progressive patients: * Patients with a histologically confirmed diagnosis of high-grade glioma regardless of molecular characterization that is recurrent or progressive. All tumors must have histologic verification at either the time of diagnosis or recurrence * Patients are only eligible after their first progression following prior surgery and radiotherapy
• ELIGIBILITY CRITERIA FOR OPTIONAL SCREENING: * Supratentorial lesion must be ≥ 1.0 cm in longest dimension and surgically accessible as determined by MRI * For patients with tumors > 4.0 cm without an adjacent cavity, the neurosurgeon must be confident that the tumor can be debulked to ≤ 4.0 cm for eligibility * Multifocal disease on the ipsilateral side is eligible if at least one catheter can be placed in all multifocal areas
• ELIGIBILITY CRITERIA FOR OPTIONAL SCREENING: Patient must be ≥ 3 at initial diagnosis but < 22 years of age at the time of enrollment on this study
• ELIGIBILITY CRITERIA FOR OPTIONAL SCREENING: Participant is willing to sign a screening consent and provide their most recent imaging to determine their potential suitability for eligibility on PBTC-061. The screening consent is to be obtained according to institutional guidelines. Telephone consent is allowable as per local guidelines and approvals. Assent, when appropriate, will be obtained according to institutional guidelines
• ELIGIBILITY CRITERIA FOR OPTIONAL SCREENING: Patients screened for this trial should be expected to meet the criteria for treatment below
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Recurrent or progressive patients: * Patients with a histologically confirmed diagnosis of high-grade glioma regardless of molecular characterization that is recurrent or progressive. All tumors must have histologic verification at either the time of diagnosis or recurrence * Patients are only eligible after their first progression following prior surgery and radiotherapy
• ELIGIBILITY CRITERIA FOR ENROLLMENT: * Supratentorial lesion must be ≥ 1.0 cm in longest dimension and surgically accessible as determined by contrast-enhanced MRI * For patients with tumors > 4.0 cm without an adjacent cavity, the neurosurgeon must be confident that the tumor can be debulked to ≤ 4.0 cm for eligibility * Multifocal disease on the ipsilateral side is eligible if at least one catheter can be placed in all multifocal areas * Tumor size will be determined using the maximal 2-dimensional cross-sectional tumor measurements, transverse x width, using either T1 images or T2/fluid attenuated inversion recovery (FLAIR) images for non-enhancing tumors * Review of these MRI scans will be necessary to determine if the tumor location and size is such that the patient may undergo biopsy and catheter placement. Eligibility imaging for the first 2 patients enrolled at each site must be sent for real-time central review. If, during screening, repeat imaging is needed for either of the first 2 patients, central review will be required for the repeated images. After the first 2 patients are enrolled, the PBTC 061 study team will be available as needed to review screening MRIs and consult with the local team
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Patient must be ≥ 3 at initial diagnosis but < 22 years of age at the time of enrollment on this study
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must have received prior surgery and radiotherapy. * Patients must have recovered from the acute treatment-related toxicities of prior treatment (defined as ≤ grade 1 if not defined in eligibility criteria; excludes alopecia) prior to enrollment * Chemotherapy ** Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea * Investigational/biologic agent or targeted therapies (non-myelosuppressive cancer therapy) ** Biologic or investigational agent (anti-neoplastic): *** Patient must have received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment **** For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur ** Monoclonal antibody treatment and agents with known prolonged half-lives: *** Patient must have received their last dose of the agent ≥ 28 days prior to study enrollment ** Immune effector cell (IEC) therapy (e.g., chimeric antigen receptor [CAR] T cells) *** For viral therapy or cellular therapy, patients must have received therapy ≥ 12 weeks prior to study enrollment * Radiation ** Patients must have had their last fraction of standard radiation ≥ 12 weeks prior to enrollment * Stem cell transplant ** Patient must be: *** ≥ 24 weeks since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease *** ≥ 12 weeks since autologous stem cell transplant prior to enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT: * Patients with neurological deficits should have deficits that are stable for a minimum of 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 * Patients with seizure disorders may be enrolled if seizures are well controlled
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Karnofsky performance scale (KPS for > 16 years of age) or Lansky performance score (LPS for ≤ 16 years of age) assessed within 7 days prior to enrollment must be ≥ 60 who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Absolute neutrophil count > 1.0 x 10^9 cells/L (laboratory values must be no older than 7 days prior to the start of therapy)
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Platelets > 100 x 10^9 cells/L (unsupported, defined as no platelet transfusion within 7 days) (laboratory values must be no older than 7 days prior to the start of therapy)
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Hemoglobin ≥ 8 g/dL (may receive transfusions) (laboratory values must be no older than 7 days prior to the start of therapy)
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (laboratory values must be no older than 7 days prior to the start of therapy)
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Prothrombin time (PT)/international normalized ratio (INR), partial thromboplastin time (PTT) ≤ 1.5 x ULN (laboratory values must be no older than 7 days prior to the start of therapy)
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) < 3 x institutional upper limit of normal (ULN) (laboratory values must be no older than 7 days prior to the start of therapy)
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Albumin ≥ 3 g/dL (laboratory values must be no older than 7 days prior to the start of therapy)
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Serum creatinine based on age/sex: * Age: 1 to < 2 years, maximum serum creatinine (mg/dL): 0.6 (male), 0.6 (female) * Age: 2 to < 6 years, maximum serum creatinine (mg/dL): 0.8 (male), 0.8 (female) * Age: 6 to < 10 years, maximum serum creatinine (mg/dL): 1 (male), 1 (female) * Age: 10 to < 13 years, maximum serum creatinine (mg/dL): 1.2 (male), 1.2 (female) * Age: 13 to < 16 years, maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female) * Age: ≥ 16 years, maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female) Patients that do not meet the criteria but have a cystatin C, 24-hour creatinine clearance or glomerular filtration rate (GFR) (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m^2 are eligible (laboratory values must be no older than 7 days prior to the start of therapy)
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (e.g., filgrastim, sargramostim, or erythropoietin). Two (2) weeks must have elapsed if the patient received a long-acting formulation
• ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study
• ELIGIBILITY CRITERIA FOR ENROLLMENT: The patient or parent/guardian can understand the consent and is willing to sign a written informed consent document according to institutional guidelines

Exclusion Criteria

• Pregnant women are excluded from this study. Female patients of childbearing potential must have a negative serum or urine pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Pregnant women are excluded from this study because G207 is an agent with the potential for teratogenic or abortifacient effects
• Lactating females are not eligible unless they have agreed not to breastfeed their infants * Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with G207, breastfeeding should be discontinued if the mother is treated with G207
• 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
• Patients with a secondary high-grade glioma are ineligible
• Patients with primary tumor involving the cerebellum, brainstem or spinal cord or that would require surgical access through a ventricle in order to deliver the prescribed protocol treatment
• Metastatic disease or diffuse, widespread, abnormal tumor pattern involving 3 or more lobes of the brain
• Tumor with evidence of clinically significant uncal herniation or midline shift, or evidence of ventricular obstruction from tumor or tonsillar herniation
• Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient’s ability to undergo surgery and/or tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results
• Known human immunodeficiency virus (HIV) seropositivity
• Diagnosis of encephalitis or central nervous system (CNS) infection < 12 weeks prior, or receiving ongoing treatment for encephalitis, CNS infection or multiple sclerosis
• Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible
• Patients who are receiving ≥ 1.5 mg of dexamethasone (or ≥ 10 mg of prednisone) daily
• Concurrent therapy with any drug active against HSV (acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir)
• Patients may not be on immunosuppressive therapy, including corticosteroids (except for patients receiving < 1.5 mg of dexamethasone or < 10 mg of prednisone daily) at time of enrollment. However, patients who require intermittent use of bronchodilators or topical steroids will not be excluded from the study
• Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to drug administration plan, other study procedures, and study restrictions
• Patients who received cranial spinal irradiation (CSI) are ineligible