VNP40101M and Temozolomide in Treating Patients With Progressive or Relapsed Malignant Glioma
- Conditions
- Brain and Central Nervous System Tumors
- Registration Number
- NCT00516282
- Lead Sponsor
- Northwestern University
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as temozolomide and VNP40101M, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Temozolomide may also stop the growth of tumor cells by blocking blood flow to the tumor.
PURPOSE: This phase I/II trial is studying the side effects and best dose of VNP40101M when given together with temozolomide and to see how well it works in treating patients with progressive or relapsed malignant glioma.
- Detailed Description
OBJECTIVES:
* To determine the maximum tolerated dose (MTD) of VNP40101M when administered with temozolomide in patients with progressive or relapsed (first relapse) malignant glioma. (Phase I)
* To record the toxicities of VNP40101M when administered with temozolomide. (Phase I and II)
* 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 II)
* 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)
OUTLINE:
* 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 14
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method MTD of CLORETAZINE At the end of phase one To determine the MTD of CLORETAZINE when administered with Temodar® in patients with malignant gliomas in first or second relapse
Progression-free survival rate End of Phase II To determine the 6 and 12 month progression-free survival rate.
- Secondary Outcome Measures
Name Time Method Toxicities of CLORETAZINE when administered with Temodar®. Adverse events are monitored at screening/baseline;day one; termination visit; followup until death. To record the toxicities of CLORETAZINE when administered with Temodar®.
(Toxicity is assessed continuously through routine medical monitoring of the patient throughout each cycle and all adverse events are recorded cumulatively on the case report forms).Response rate to CLORETAZINE after Temodar® in patients with malignant gliomas in first or second relapse Day one of every cycle To determine the response rate to CLORETAZINE after Temodar® in patients with malignant gliomas in first or second relapse.
Record the toxicities of CLORETAZINE when administered after Temodar Continuously after the first dose;within thirty days of each administration of investigational agent To record the toxicities of CLORETAZINE when administered after Temodar®
MGMT Methylation Status Baseline and day seven of every cycle To determine MGMT methylation status as well as other methylation patterns in blood correlate with outcome.
Determine overall survival All patients will be followed until death To determine overall survival.
Measure the level of AGT expression Day seven of every cycle To measure the level of AGT expression in peripheral blood monocytes before treatment with Temodar® and just prior to the administration of CLORETAZINE.
CSF penetration of CLORETAZINE Day seven of cycle one of Phase 2 only To determine CSF penetration of CLORETAZINE once the MTD is reached from phase I and correlate with serum/plasma PK
Trial Locations
- Locations (2)
Northwestern University
🇺🇸Chicago, Illinois, United States
Hematology-Oncology Associates of Illinois
🇺🇸Chicago, Illinois, United States