VNP40101M and Temozolomide in Treating Patients With Progressive or Relapsed Malignant Glioma
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|ClinicalTrials.gov Identifier: NCT00516282|
Recruitment Status : Terminated (The pharmaceutical collaborator filed for bankruptcy and as a result, the study was unable to move into the phase II portion.)
First Posted : August 15, 2007
Last Update Posted : August 26, 2011
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.
|Condition or disease||Intervention/treatment||Phase|
|Brain and Central Nervous System Tumors||Drug: CLORETAZINE Drug: temozolomide||Phase 1|
- 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)
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Cloretazine® (VNP40101M) and Temodar® (Temozolomide) for Patients With Malignant Glioma in First Relapse or Progression|
|Study Start Date :||August 2007|
|Actual Primary Completion Date :||October 2009|
|Actual Study Completion Date :||October 2009|
- Drug: CLORETAZINE
CLORETAZINE will be administered intravenously on day 7. The starting dose of CLORETAZINE will be 100 mg/m2 given within 3 hours after the last dose of Temodar on day 7. CLORETAZINE will be given as an IV infusion over 15-30 minutes via a freely flowing peripheral or central intravenous line. CLORETAZINE will be escalated by 50 mg/m2 for the second cohort then by 25 mg/m2 increments in the following cohorts of 3-6 patients using a standard phase I trial design until a MTD is determined. If dose level 2 has two DLTs then patients will be accrued to a new dose level of 125 mg/m2. Prior to receiving Cloretazine, blood will be drawn for gene methylation studies.Other Name: VNP40101M
- Drug: temozolomide
Temozolomide will be given orally at a dose of 75mg/m2 daily on day 1 through 7. There will be no dose modification for this agent. Prior to receiving Temozolomide, blood will be drawn for gene methylation studies.Other Name: Temodar
- MTD of CLORETAZINE [ Time Frame: 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 [ Time Frame: End of Phase II ]To determine the 6 and 12 month progression-free survival rate.
- Toxicities of CLORETAZINE when administered with Temodar®. [ Time Frame: 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).
- MGMT Methylation Status [ Time Frame: 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 [ Time Frame: All patients will be followed until death ]To determine overall survival.
- Response rate to CLORETAZINE after Temodar® in patients with malignant gliomas in first or second relapse [ Time Frame: 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 [ Time Frame: Continuously after the first dose;within thirty days of each administration of investigational agent ]To record the toxicities of CLORETAZINE when administered after Temodar®
- Measure the level of AGT expression [ Time Frame: 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 [ Time Frame: 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00516282
|United States, Illinois|
|Hematology-Oncology Associates of Illinois|
|Chicago, Illinois, United States, 60611-2998|
|Chicago, Illinois, United States, 60611-3013|
|Principal Investigator:||Jeffrey Raizer, MD||Northwestern University|