MK0752 in Treating Young Patients With Recurrent or Refractory CNS Cancer

This study has been terminated.
(This Phase I study was permanently closed to patient accrual on February 23, 2011, due to the discontinuation of support from MERCK.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:
NCT00572182
First received: December 11, 2007
Last updated: March 2, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: MK-0752
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of MK-0752 in Pediatric Patients With Recurrent or Refractory CNS Malignancies

Resource links provided by NLM:


Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: First 28 days of treatment ] [ Designated as safety issue: Yes ]
  • MK0752 systemic exposure [ Time Frame: Day 1 of course 1 ] [ Designated as safety issue: No ]
    Serial blood samples for pharmacokinetic studies of MK-0752 will be collected with the first dose of course 1 at pre-specified times.


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: Day 1 of course 1 ] [ Designated as safety issue: No ]
    Serial blood samples for pharmacokinetic studies of MK-0752 will be collected with the first dose of course 1 at pre-specified times.

  • Toxicity [ Time Frame: From day 1 of treatment until off study ] [ Designated as safety issue: Yes ]
  • Objective response rate [ Time Frame: End of courses 2, 4, 6 and at the end of treatment ] [ Designated as safety issue: No ]
    Brain imaging to assess tumor response to the treatment is performed at baseline, at the end of courses 2, 4, 6 and at the end of therapy.


Enrollment: 33
Study Start Date: July 2008
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: MK-0752
    This is a dose escalation study. Patients may receive 150, 200, 260 or 325 mg/m2 orally for 3 consecutive days of every 7 days for 28 days (dosing regimen 1 - closed to accrual 2/23/2010) or 800, 1000, 1400, or 1800 mg/m2 orally once weekly for 28 days (1 course). In the absence of unacceptable toxicity or disease progression, treatment may continue for 6 courses.
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

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00572182

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Maryland
NCI - Pediatric Oncology Branch
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
Investigators
Study Chair: Maryam Fouladi, MD Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided

Responsible Party: Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT00572182     History of Changes
Obsolete Identifiers: NCT00923208
Other Study ID Numbers: CDR0000578114, U01CA081457, PBTC-024, NCI-09-C-0112
Study First Received: December 11, 2007
Last Updated: March 2, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pediatric Brain Tumor Consortium:
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

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases

ClinicalTrials.gov processed this record on September 18, 2014