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

Phase 1
3 Years
21 Years
Not Enrolling
Brain and Central Nervous System Tumors

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Trial Information

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



- To estimate the maximum tolerated dose (MTD) and recommended phase II dose of MK0752
administered for 3 consecutive days of every 7 days in 28 day courses to young patients
with recurrent or refractory CNS malignancies (Dosing regimen 1 - closed to accrual

- To estimate the MTD and recommend a phase II dose of MK0752 administered once weekly in
28 day courses to young patients with recurrent or refractory CNS malignancies (Dosing
regimen 2).

- To compared the MK0752 systemic exposure attained with each dosage level on the
different dosing regimens.


- To characterize the pharmacokinetics of MK0752.

- To document and describe toxicities associated with MK0752.

- To preliminarily define the antitumor activity of MK0752 within the confines of a phase
I setting.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive oral MK0752 once daily on days 1-3, 8-10, 15-17, and 22-24 (dosing regimen
1 - closed to accrual 2/23/2010) or days 1, 8, 15, and 22 (dosing regimen 2). Treatment
repeats every 28 days for up to 6 courses in the absence of disease progression or
unacceptable toxicity. Treatment may be extended up to 19 courses if the patient is
benefitting from the treatment.

Patients undergo blood sample collection periodically for pharmacokinetic studies.

After completion of study treatment, patients are followed for 30 days.

Inclusion Criteria


- 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)


- 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


- Recovered from the acute toxic effects of all prior therapy

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Time Frame:

First 28 days of treatment

Safety Issue:


Principal Investigator

Maryam Fouladi, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital Medical Center, Cincinnati


United States: Food and Drug Administration

Study ID:




Start Date:

July 2008

Completion Date:

February 2011

Related Keywords:

  • Brain and Central Nervous System Tumors
  • recurrent childhood brain stem glioma
  • childhood central nervous system germ cell tumor
  • recurrent childhood cerebellar astrocytoma
  • recurrent childhood cerebral astrocytoma
  • childhood high-grade cerebral astrocytoma
  • childhood choroid plexus tumor
  • childhood craniopharyngioma
  • recurrent childhood ependymoma
  • recurrent childhood medulloblastoma
  • childhood oligodendroglioma
  • recurrent childhood pineoblastoma
  • recurrent childhood supratentorial primitive neuroectodermal tumor
  • childhood atypical teratoid/rhabdoid tumor
  • childhood spinal cord neoplasm
  • childhood infratentorial ependymoma
  • childhood supratentorial ependymoma
  • recurrent childhood visual pathway and hypothalamic glioma
  • childhood grade III meningioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
Duke Comprehensive Cancer Center Durham, North Carolina  27710
Children's National Medical Center Washington, District of Columbia  20010-2970
Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania  15213
Children's Memorial Hospital - Chicago Chicago, Illinois  60614
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute Boston, Massachusetts  02115
NCI - Pediatric Oncology Branch Bethesda, Maryland  
Dan L. Duncan Cancer Center at Baylor College of Medicine Houston, Texas  77030
Seattle Children's Hospital Seattle, Washington  98105