A Phase I Study of MK-0752 in Pediatric Patients With Recurrent or Refractory CNS Malignancies

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed primary CNS tumor

- Patients with intrinsic brain stem tumors do not require histologic
verification, but must have radiographic evidence of progression

- Recurrent disease or refractory to standard therapy

- No histologically benign brain tumors (e.g., low-grade glioma)

PATIENT CHARACTERISTICS:

- Karnofsky performance status (PS) or Lansky PS 60-100%

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Absolute neutrophil count ≥ 1,000/μL

- Platelet count ≥ 100,000/μL (unsupported)

- Hemoglobin ≥ 8 g/dL (RBC transfusions allowed)

- Creatinine clearance OR glomerular filtration rate ≥ 70 mL/min OR serum creatinine
based on age as follows:

- 0.8 mg/dL (≤ 5 years of age)

- 1.0 mg/dL (> 5 to ≤ 10 years of age)

- 1.2 mg/dL (> 10 to ≤ 15 years of age)

- 1.5 mg/dL (> 15 years of age)

- Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

- ALT ≤ 2.5 times ULN for age

- Albumin ≥ 2.5 g/dL

- Sodium, potassium, magnesium, and calcium normal

- Patients with neurological deficits are eligible provided these deficits are stable
for ≥ 2 weeks prior to study registration

- No clinically significant systemic illness (e.g., serious infection or significant
cardiac, pulmonary, hepatic, or other organ dysfunction) that would compromise the
patient's ability to tolerate study therapy or would likely interfere with the study
procedures or results

- No known hypersensitivity to MK0752

PRIOR CONCURRENT THERAPY:

- Recovered from the acute toxic effects of all prior therapy

- At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for
nitrosoureas)

- At least 7 days since prior investigational or biologic agents

- At least 3 weeks since prior investigational or biologic agents that have a
prolonged half-life or for which the patient has experienced ≥ grade 2
myelosuppression in the treatment course preceding discontinuation of therapy

- At least 3 half lives since prior monoclonal antibody therapy

- At least 6 months since prior total body irradiation or craniospinal radiotherapy

- At least 6 weeks since other prior substantial bone marrow irradiation

- At least 2 weeks since prior local palliative radiotherapy (small volume)

- At least 6 months since prior allogeneic bone marrow transplantation (BMT)

- No evidence of active graft versus host disease

- At least 3 months since prior autologous BMT or stem cell transplantation

- At least 7 days since prior hematopoietic growth factors (filgrastim [G-CSF],
sargramostim [GM-CSF], or erythropoietin) (14 days for long-acting formulations)

- No prior MK0752

- No concurrent enzyme-inducing anticonvulsant drugs (EIACDs)

- No other concurrent anticancer or investigational drug therapy

- Concurrent dexamethasone allowed provided patient is on a stable or decreasing dose
for ≥ 2 weeks prior to study registration