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

Phase 1
Completed
Conditions
Brain and Central Nervous System Tumors
Registration Number
NCT00098761
Lead Sponsor
Pediatric Brain Tumor Consortium
Brief 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
42
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Estimate the maximum tolerated doseFirst 6 weeks of therapy
Number of participants with dose limiting toxicitiesFirst 6 weeks of therapy
Secondary Outcome Measures
NameTimeMethod
PharmacokineticsDay 1 of therapy

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 VNP40101MPrior to course 3, 5, and 7 and end of therapy

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

Trial Locations

Locations (10)

Children's Memorial Hospital - Chicago

🇺🇸

Chicago, Illinois, United States

UCSF Comprehensive Cancer Center

🇺🇸

San Francisco, California, United States

Duke Comprehensive Cancer Center

🇺🇸

Durham, North Carolina, United States

Children's National Medical Center

🇺🇸

Washington, District of Columbia, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

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

🇺🇸

Boston, Massachusetts, United States

Children's Hospital of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

St. Jude Children's Research Hospital

🇺🇸

Memphis, Tennessee, United States

Children's Hospital and Regional Medical Center - Seattle

🇺🇸

Seattle, Washington, United States

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

🇺🇸

Houston, Texas, United States

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