Clinical trial NCT00572182: MK0752 in Treating Young Patients With Recurrent or Refractory CNS Cancer
Official title: A Phase I Study of MK-0752 in Pediatric Patients With Recurrent or Refractory CNS Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Keywords: 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
Lead sponsor: Pediatric Brain Tumor Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-12-12
Enrollment: 33
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: MK0752 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of MK0752 in treating young patients with recurrent or refractory CNS cancer.

Detailed description: OBJECTIVES:

Primary

* 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 2/23/2010).
* 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.

Secondary

* 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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: First 28 days of treatment
measure: MK0752 systemic exposure
timeFrame: Day 1 of course 1
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: Day 1 of course 1
measure: Toxicity
timeFrame: From day 1 of treatment until off study
measure: Objective response rate
timeFrame: End of courses 2, 4, 6 and at the end of treatment
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Children's Memorial Hospital - Chicago
state: Illinois
city: Bethesda
country: United States
facility: NCI - Pediatric Oncology Branch
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
state: Massachusetts
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Dan L. Duncan Cancer Center at Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Maryam Fouladi, MD
role: STUDY_CHAIR
References: