A Phase I/II Trial of Cloretazine® (VNP40101M) and Temodar® (Temozolomide) for Patients With Malignant Glioma in First Relapse or Progression
- To determine the maximum tolerated dose (MTD) of VNP40101M when administered with
temozolomide in patients with progressive or relapsed (first relapse) malignant glioma.
- To record the toxicities of VNP40101M when administered with temozolomide. (Phase I and
- To measure the level of AGT expression in peripheral blood monocytes before treatment
with temozolomide and just prior to the administration of VNP40101M. (Phase I and II)
- To determine MGMT methylation status as well as other methylation patterns in blood and
tissue from patients treated with this regimen and correlate with outcome. (Phase I and
- To determine the 6- and 12-month progression-free survival rates of patients treated
with this regimen. (Phase II)
- To determine overall survival of patients treated with this regimen. (Phase II)
- To determine the complete and partial response rates in patients treated with this
regimen. (Phase II)
- To determine CSF penetration of VNP40101M once the MTD is reached from phase I and
correlate with serum/plasma pharmacokinetics. (Phase II)
- Phase I: Patients receive oral temozolomide on days 1-7 and VNP40101M IV over 15-30
minutes 2 hours after the last dose of temozolomide on day 7. Treatment repeats every 7
weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of VNP40101M until the maximum tolerated
dose (MTD) is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose limiting toxicity.
- Phase II: Patients receive oral temozolomide and VNP40101M as in phase I. VNP40101M is
given at the MTD determined in phase I.
In both phases, patients complete the Functional Assessment of Cancer Therapy-Brain
(FACT-BR) questionnaire on day 1 of each course.
Blood is collected for in vitro isolation of mononuclear cells for analysis of O^6
alkylguanine DNA alkyltransferase on days 1 and 7 of course 1. Blood, plasma, CSF, and
formalin-fixed paraffin-embedded tissue blocks are collected for gene methylation studies,
including MGMT, at baseline and on day 1 of each course.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of CLORETAZINE
To determine the MTD of CLORETAZINE when administered with Temodar® in patients with malignant gliomas in first or second relapse
At the end of phase one
Jeffrey Raizer, MD
United States: Food and Drug Administration
|Hematology-Oncology Associates of Illinois||Chicago, Illinois 60611-2998|
|Northwestern University||Chicago, Illinois 60611|