VNP40101M in Treating Young Patients 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.
|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|
- 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 ]
- 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
|Study Start Date:||February 2005|
|Study Completion Date:||February 2008|
|Primary Completion Date:||October 2006 (Final data collection date for primary outcome measure)|
- Determine the maximum tolerated dose and dose-limiting toxicity of VNP40101M in pediatric patients with recurrent, progressive, or refractory primary brain tumors.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00098761
|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|
|Study Chair:||Sri Gururangan, MRCP (UK)||Duke University|