Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Patients meeting the following inclusion criteria will be eligible for the study:

Patient must be ≥ 3 at initial diagnosis but < 22 years of age at the time of enrollment on this study.
Patients must have 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
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/FLAIR images for non-enhancing tumors.
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 received prior surgery and radiotherapy and recovered from the acute treatment related toxicities (defined as ≤ Grade 1 if not defined in eligibility criteria; excludes alopecia) prior to enrollment.
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
Myelosuppressive 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 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 their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment.

o 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.

Immune Effector Cell (IEC) Therapy (e.g., CAR T cells) For viral therapy or cellular therapy, patients must have received therapy ≥ 3 months prior to study enrollment.
Stem Cell Transplant: Patient must be:
≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease.
≥ 3 months since autologous stem cell transplant prior to enrollment.

Neurologic Status:

Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment.

o 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.
Patients must have adequate organ and marrow function as defined below:
Absolute neutrophil count > 1.0 x 109 cells/L
Platelets > 100 x 109 cells/L (unsupported, defined as no platelet transfusion within 7 days)
Hemoglobin ≥ 8 g/dL (may receive transfusions)
Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
PT/INR, PTT ≤ 1.5 x ULN
ALT(SGPT) and AST (SGOT) < 3 x institutional upper limit of normal (ULN)
Albumin ≥ 3 g/dL
Serum creatinine based on age/gender as noted in Table 2. Patients that do not meet the criteria in Table 2 but have a Cystatin C, 24-hour Creatinine Clearance or GFR (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m2 are eligible.

Age Maximum Serum Creatinine (mg/dL) Male Female 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4

≥ 16 years 1.7 1.4

Corticosteroids Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment.

Growth Factors 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.

Pregnancy Prevention 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.

Exclusion Criteria:

Pregnant women are excluded from this study. Lactating females are not eligible unless they have agreed not to breastfeed their infants

Concurrent Illness

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 HIV seropositivity.
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.
Patient 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
Diagnosis of encephalitis or CNS infection < 3 months prior, or receiving ongoing treatment for encephalitis, CNS infection or multiple sclerosis

Concomitant Medications

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.

Inability to participate 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.

Other Infectious Diseases Patients who are known to be HIV seropositive are ineligible. Patient must have documented evidence of negative tests for the presence of Human Immunodeficiency Virus (HIV).

Prior Cranial Spinal Irradiation Patients who received cranial spinal irradiation (CSI) are ineligible.