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

December 11, 2007
March 2, 2012
July 2008
February 2011   (final data collection date for primary outcome measure)
  • 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.
Maximum tolerated dose (MTD) and recommended phase II dose of MK0752
Complete list of historical versions of study NCT00572182 on ClinicalTrials.gov Archive Site
  • 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.
  • Pharmacokinetics
  • Toxicity
  • Antitumor activity
Not Provided
Not Provided
 
MK0752 in Treating Young Patients With Recurrent or Refractory CNS Cancer
A Phase I Study of MK-0752 in Pediatric Patients With Recurrent or Refractory CNS Malignancies

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
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.
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
33
February 2011
February 2011   (final data collection date for primary outcome measure)

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
Both
3 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00572182
CDR0000578114, U01CA081457, PBTC-024, NCI-09-C-0112
Yes
Pediatric Brain Tumor Consortium
Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
Study Chair: Maryam Fouladi, MD Children's Hospital Medical Center, Cincinnati
Pediatric Brain Tumor Consortium
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP