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Brain and Central Nervous System TumorsPhase 1NCT00098761

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

A Phase 1 study testing laromustine in people with Brain and Central Nervous System Tumors, run by Pediatric Brain Tumor Consortium at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 more about this study

Who is it for?
Ages Up to 21 years
Conditions the study is for
Brain and Central Nervous System Tumors
What is being tested?
laromustine
Type of treatment
Injection or infusion
How many people
42 participants
Where
10 sitesUnited States
Study dates
Feb 2005to Feb 2008
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

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

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

  • Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

    Houston, Texas, 77030-2399

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104-4318

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • UCSF Comprehensive Cancer Center

    San Francisco, California, 94115

  • Children's Hospital and Regional Medical Center - Seattle

    Seattle, Washington, 98105

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

Other trials in United States

About this study

Official title: Phase I Study Of Cloretazine (VNP40101M) In Children With Recurrent, Progressive Or Refractory Primary Brain Tumors

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.

Being tested
laromustine
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
Medical subject headings
Central Nervous System Neoplasms, Optic Nerve Glioma, Astrocytoma, Familial ependymoma, Medulloblastoma, Choroid Plexus Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • laromustineDrug

    Also called Cloretazine, VNP40101M

    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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Estimate the maximum tolerated dose

    Measured: First 6 weeks of therapy

  2. Number of participants with dose limiting toxicities

    Measured: First 6 weeks of therapy

Secondary outcomes (2)

  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.

    Measured: 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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2004 (estimated)
  2. Study startFeb 2005
  3. Primary completionOct 2006
  4. Study completionFeb 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00098761
Sponsor's protocol ID
CDR0000396779
Other IDs
PBTC-017, VION-VNP40101M
Status last verified
Jun 2011
First submitted
8 Dec 2004
Last updated
30 Jun 2011
Results posted
No
Data monitoring committee
Yes

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing laromustine in people with Brain and Central Nervous System Tumors, run by Pediatric Brain Tumor Consortium at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Estimate the maximum tolerated dose (time frame: First 6 weeks of therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00098761, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2011.

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