VNP40101M in Treating Young Patients With Recurrent, Progressive, or Refractory Primary Brain Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:
NCT00098761
First received: December 8, 2004
Last updated: June 29, 2011
Last verified: June 2011
  Purpose

RATIONALE: Drugs used in chemotherapy, such as VNP40101M, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of VNP40101M in treating young patients with recurrent, progressive, or refractory primary brain tumors.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: laromustine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study Of Cloretazine (VNP40101M) In Children With Recurrent, Progressive Or Refractory Primary Brain Tumors

Resource links provided by NLM:


Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:
  • Estimate the maximum tolerated dose [ Time Frame: First 6 weeks of therapy ] [ Designated as safety issue: Yes ]
  • Number of participants with dose limiting toxicities [ Time Frame: First 6 weeks of therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: Day 1 of therapy ] [ Designated as safety issue: No ]
    Plasma samples for pharmacokinetic studies will be collected with the first dose of the study drug pre-infusion, and 5, 15, and 30 minutes, 1 hour, 2 hours, and 4 hours after the end of infusion. VNP40101M plasma concentration-time data will be modeled and the individual pharmacokinetic pararmeters volume of the central compartment, elimination rate constant, and half-life will be estimated.

  • Tumor response to VNP40101M [ Time Frame: Prior to course 3, 5, and 7 and end of therapy ] [ Designated as safety issue: No ]
    MRI of the brain will be obtained prior to couses 3, 5, and 7 and at the end of therapy


Enrollment: 42
Study Start Date: February 2005
Study Completion Date: February 2008
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: laromustine
    This is a dose escalation study. Participants receive 20, 30, 45, 60, 78, 103, 137, 182, or 242 mg/m2/day intravenously over 30 minutes for 5 consecutive days every 6 weeks up to 48 weeks.
    Other Names:
    • Cloretazine
    • VNP40101M
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose and dose-limiting toxicity of VNP40101M in pediatric patients with recurrent, progressive, or refractory primary brain tumors.

Secondary

  • Determine the pharmacokinetics of this drug and its active metabolite VNP4090CE in these patients.
  • Determine the efficacy of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to receiving ≥ 1 of the following prior therapies: craniospinal irradiation (yes vs no), autologous bone marrow transplant (yes vs no), and > 2 myelosuppressive chemotherapy or myelosuppressive biologic therapy regimens (yes vs no).

Patients receive VNP40101M IV over 30 minutes on days 1-5. Treatment repeats every 42 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 2-6 patients per stratum receive escalating doses of VNP40101M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD.

Patients are followed for 3 months.

PROJECTED ACCRUAL: A total of 4-60 patients (2-30 per stratum) will be accrued for this study within 18 months.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed* primary brain tumor, including benign brain tumors (e.g., low-grade glioma)

    • Recurrent or progressive disease OR refractory to standard therapy NOTE: *Patients with intrinsic brain stem or diffuse optic pathway tumors do not require histological confirmation, but must have clinical and/or radiographic evidence of disease progression
  • No bone marrow disease

PATIENT CHARACTERISTICS:

Age

  • 21 and under

Performance status

  • Karnofsky 50-100% (for patients > 16 years of age) OR
  • Lansky 50-100% (for patients ≤ 16 years of age)

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3*
  • Platelet count ≥ 100,000/mm^3*
  • Hemoglobin ≥ 8 g/dL* NOTE: *Unsupported

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT and AST ≤ 2.5 times ULN
  • No overt hepatic disease

Renal

  • BUN < 25 mg/dL
  • Creatinine ≤ 1.5 times ULN for age OR
  • Glomerular filtration rate > 70 mL/min
  • No overt renal disease

Cardiovascular

  • Shortening fraction ≥ 30% by echocardiogram OR
  • Ejection fraction ≥ 50% by gated radionucleotide study
  • No clinically significant cardiac arrhythmia by EKG
  • No overt cardiac disease

Pulmonary

  • DLCO ≥ 60% of predicted
  • Chest X-ray normal (defined as absence of pulmonary infiltrates, pneumonitis, pleural effusion, pulmonary hemorrhage, or fibrosis) AND a resting pulse oximetry reading of > 94% in room air (for patients who cannot perform the DLCO)
  • No overt pulmonary disease

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Neurologic deficits allowed provided there has been no deficit progression for ≥ 1 week before study entry
  • No uncontrolled infection
  • No known hypersensitivity to polyethylene glycol

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • At least 6 months since prior allogeneic bone marrow or stem cell transplantation
  • At least 3 months since prior autologous bone marrow or stem cell transplantation
  • More than 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
  • At least 3 weeks since prior myelosuppressive anticancer biologic therapy
  • No concurrent routine colony-stimulating factors

Chemotherapy

  • At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

  • Concurrent corticosteroids allowed provided dose is stable or decreasing for ≥ 1 week before study entry

Radiotherapy

  • At least 3 months since prior craniospinal irradiation ≥ 18 Gy
  • At least 2 weeks since prior focal irradiation to the primary tumor and/or symptomatic metastatic sites

Surgery

  • Not specified

Other

  • At least 7 days since prior nonmyelosuppressive anticancer therapy
  • At least 7 days since prior investigational agents
  • Concurrent enzyme-inducing anticonvulsant drugs allowed
  • No other concurrent anticancer or experimental agents or therapies
  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: NCT00098761

Locations
United States, California
UCSF 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, 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, 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
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
Investigators
Study Chair: Sri Gururangan, MRCP (UK) Duke University
  More Information

Additional Information:
Publications:
Responsible Party: James M. Boyett/PBTC Operations and Biostatistics Center Executive Director, Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT00098761     History of Changes
Other Study ID Numbers: CDR0000396779, PBTC-017, VION-VNP40101M
Study First Received: December 8, 2004
Last Updated: June 29, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pediatric Brain Tumor Consortium:
recurrent childhood brain stem glioma
recurrent childhood visual pathway and hypothalamic glioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood ependymoma
recurrent childhood medulloblastoma
recurrent childhood supratentorial primitive neuroectodermal tumor
childhood central nervous system germ cell tumor
childhood choroid plexus tumor
childhood craniopharyngioma
childhood infratentorial ependymoma
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
childhood high-grade cerebral astrocytoma
childhood low-grade cerebral astrocytoma

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

ClinicalTrials.gov processed this record on July 24, 2014