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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
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.
UCSF Comprehensive Cancer Center
San Francisco, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States
Estimate the maximum tolerated dose
Time frame: First 6 weeks of therapy
Number of participants with dose limiting toxicities
Time frame: First 6 weeks of therapy
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
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States
Duke Comprehensive Cancer Center
Durham, North Carolina, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States