Enzastaurin in Treating Young Patients With Refractory Primary CNS Tumors

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring recurrent childhood brain stem glioma, childhood central nervous system germ cell tumor, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, childhood choroid plexus tumor, childhood craniopharyngioma, childhood infratentorial ependymoma, childhood supratentorial ependymoma, recurrent childhood ependymoma, recurrent childhood medulloblastoma, childhood oligodendroglioma, recurrent childhood supratentorial primitive neuroectodermal tumor, recurrent childhood visual pathway and hypothalamic glioma, recurrent childhood visual pathway glioma, childhood grade I meningioma, childhood grade II meningioma, childhood grade III meningioma, recurrent childhood subependymal giant cell astrocytoma, recurrent childhood pineoblastoma, recurrent childhood brain tumor, disseminated neuroblastoma, recurrent neuroblastoma Read More

DISEASE CHARACTERISTICS:

• Histologically confirmed primary CNS malignancy including low-grade glioma

  • All tumors, except intrinsic brain stem and diffuse optic pathway tumors, must have histological verification at either the time of diagnosis or recurrence

    • Patients with intrinsic brain stem or diffuse optic pathway tumors must have clinical and/or radiographic evidence of progression
• Recurrent or progressive disease or disease refractory to standard therapy and for which there is no known curative therapy

PATIENT CHARACTERISTICS:

Inclusion Criteria:

• Karnofsky performance scale (for > 16 years of age) or Lansky performance score (for ≤ 16 years of age) ≥ 60% assessed within two weeks prior to registration
• Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL
• Platelet count ≥ 100,000/μL (transfusion independent)
• Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)

• Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine based on age as follows:

  • 0.8 mg/dL (≤ 5 years of age)
  • 1.0 mg/dL (6 to 10 years of age)
  • 1.2 mg/dL (11 to 15 years of age)
  • 1.5 mg/dL (≥ 16 years of age)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
• ALT ≤ 5 x ULN for age
• Serum albumin ≥ 2.5 g/dL
• 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
• Negative pregnancy test
• Patients must have a normal QTc for age and no evidence of a clinically significant arrhythmia on ECG
• No evidence of active graft-versus-host disease

Exclusion Criteria:

• Pregnant or lactating
• Body surface area < 0.5 m^2
• Clinically significant unrelated systemic illness that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results
• Known hypersensitivity to enzastaurin hydrochloride or its components
• Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy

PRIOR CONCURRENT THERAPY:

Inclusion Criteria:

• Must have recovered from the acute toxic effects (grade ≤ 2) of all prior therapy before entering this study
• Must not have received myelosuppressive chemotherapy within 3 weeks of entry onto this study (6 weeks for prior nitrosourea)

• At least 7 days since the completion of therapy with a hematopoietic growth agent (i.e., filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin)

  • At least 14 days since long-acting formulations
  • Therapeutic use of myeloid growth factors in patients with serious neutropenic conditions, such as sepsis, may be considered at the investigator's discretion
• At least 7 days since the completion of therapy with a biologic agent
• At least 2 weeks since prior local palliative radiotherapy (small port)
• At least 6 months must have elapsed after prior total body irradiation (TBI) or craniospinal radiotherapy
• At least 6 weeks must have elapsed after other substantial bone marrow irradiation
• At least 6 months since prior allogeneic bone marrow transplantation
• At least 3 months since prior autologous bone marrow or stem cell transplantation

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

  • Corticosteroids should be used at the lowest dose to control symptoms of edema and mass effect

Exclusion Criteria:

• Routine concurrent use of growth factors (i.e., G-CSF, GM-CSF, or erythropoietin)
• Any other concurrent anticancer or investigational drug therapy
• Concurrent enzyme-inducing anticonvulsants (EIACDs)
• Concurrent gents that prolong the QTc
• Concurrent drugs that are substrates or inhibitors of CYP3A4 or CYP2C9
• Other concurrent drugs that are sensitive substrates of CYP2C8, CYP2C9, or CYP2C19 and/or have a narrow therapeutic window