Phase I Study Of Cloretazine (VNP40101M) In Children With Recurrent, Progressive Or Refractory Primary Brain Tumors
- 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
- 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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Estimate the maximum tolerated dose
First 6 weeks of therapy
Sri Gururangan, MRCP (UK)
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|UCSF Comprehensive Cancer Center||San Francisco, California 94115|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital||Houston, Texas 77030-2399|