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CompletedNCT00098761Updated Jun 30, 2011

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

A Phase 1 interventional study of laromustine in Brain and Central Nervous System Tumors, sponsored by Pediatric Brain Tumor Consortium. Completed at 10 sites in United States. Open to participants aged Up to 21 Years. Per ClinicalTrials.gov, last updated 2011-06-30.

Sponsored by Pediatric Brain Tumor Consortium · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
42
Allocation
Not applicable
Ages
Up to 21 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Brain and Central Nervous System Tumors

Keywords

  • 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
03

In context

Brain Neoplasms

1,960 studies on the registry are indexed under Brain Neoplasms; 516 are open to participants now.

This study's enrollment of 42 is close to the median of 40 across 1,458 interventional studies indexed under Brain Neoplasms.

Browse Brain Neoplasms studies →

Lead sponsor

Pediatric Brain Tumor Consortium is the lead sponsor of 31 studies on the registry; none are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 4 (80%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 21 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
42 participants (actual)

Interventions

  • Druglaromustine

    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.

    Also known as: Cloretazine, VNP40101M

06

What researchers measure

Primary outcomes

  1. Estimate the maximum tolerated dose

    Time frame: First 6 weeks of therapy

  2. Number of participants with dose limiting toxicities

    Time frame: First 6 weeks of therapy

Secondary outcomes

  1. Pharmacokinetics

    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.

    Time frame: Day 1 of therapy

  2. Tumor response to VNP40101M

    MRI of the brain will be obtained prior to couses 3, 5, and 7 and at the end of therapy

    Time frame: Prior to course 3, 5, and 7 and end of therapy

07

Study locations

10 sites
  • UCSF Comprehensive Cancer Center
    San Francisco, California 94115, United States
  • Children's National Medical Center
    Washington, District of Columbia 20010-2970, United States
  • Children's Memorial Hospital - Chicago
    Chicago, Illinois 60614, United States
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • Duke Comprehensive Cancer Center
    Durham, North Carolina 27710, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104-4318, United States
  • Children's Hospital of Pittsburgh
    Pittsburgh, Pennsylvania 15213, United States
  • St. Jude Children's Research Hospital
    Memphis, Tennessee 38105, United States
  • Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
    Houston, Texas 77030-2399, United States
  • Children's Hospital and Regional Medical Center - Seattle
    Seattle, Washington 98105, United States
08

References and documents

Publications

  • Gururangan S, Turner CD, Stewart CF, O'Shaughnessy M, Kocak M, Poussaint TY, Phillips PC, Goldman S, Packer R, Pollack IF, Blaney SM, Karsten V, Gerson SL, Boyett JM, Friedman HS, Kun LE. Phase I trial of VNP40101M (Cloretazine) in children with recurrent brain tumors: a pediatric brain tumor consortium study. Clin Cancer Res. 2008 Feb 15;14(4):1124-30. doi: 10.1158/1078-0432.CCR-07-4242. PubMed 18281546 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 30, 2011, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00098761
Lead sponsor
Pediatric Brain Tumor Consortium
Collaborators
National Cancer Institute (NCI)
First posted
Dec 9, 2004
Start date
Feb 2005
Primary completion
Oct 2006
Completion
Feb 2008
Last update
Jun 30, 2011

Study contacts

Sri Gururangan, MRCP (UK)
study chair · Duke University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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