Enzastaurin in Treating Young Patients With Refractory Primary CNS Tumors

• Status: Completed
• Trial end date: 2010-05-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Enzastaurin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and best dose of enzastaurin in treating young patients with refractory primary brain tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pediatric Brain Tumor Consortium
• Collaborator: National Cancer Institute (NCI)

Criteria

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