Ignite Creation Date:
2024-05-05 @ 12:03 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00224978
Status:
COMPLETED
Last Update Posted:
2009-11-18
First Post:
2005-09-21
Brief Title:
Chloroquine for Treatment of Glioblastoma Multiforme
Sponsor:
National Institute of Neurology and Neurosurgery Mexico
Organization:
National Institute of Neurology and Neurosurgery Mexico
Study Overview
Official Title:
Chloroquine as Adjuvant to the Treatment of Glioblastoma Multiforme A Randomized Trial
Status:
COMPLETED
Status Verified Date:
2009-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Chloroquine is a strong lysosomotropic and DNA-intercalating agent in experimental studies Neurosurgical Focus 142 February 2003 and an open-label clinical trial the investigators have demonstrated a strong adjuvant effect of chloroquine on the therapy of malignant gliomas This study will assess in a randomized placebo-controlled double-blind study the effects of chloroquine as adjuvant to the conventional therapy of Glioblastoma Multiforme
Detailed Description:
ANTECEDENTS We have shown experimentally a significant adjuvant effect of quinacrine an analog of chloroquine on cultured malignant glial cells and C6 implanted malignant glioma in Wistar rats When quinacrine was added to the standard therapy with carmustine cell destruction and tumor diminution were higher than therapy with carmustine alone Those results were published in Neurosurgery 2001 49969-973 at that time the manuscript was in press
The present protocol started with a controlled open-label clinical trial on 7 patients with GBM and 7 contemporary control patients All patients received the same treatment of extensive surgery carmustine therapy and irradiation at the standard doses as as described in our previous report Surgical Neurology 2000 53157-162 Once selected to enter the study the patients were allocated alternatively in the chloroquine or the control group Endpoint evaluation was settled as surviving time after the beginning of therapy and the end point follow-up was settled in survivors at two years after the beginning of treatment
18 months after the beginning of the open trial it was observed that chloroquine treated patients had a longer survival and no adverse effects to chloroquine therapy were seen
At that time it was decided to start the second part of the protocol designed as a double-blind placebo-controlled trial ideal number of patients to be included was settled in 15 patients on each group
The results of the 1st phase of the study by the open-label trial were published in Neurosurgical Focus httpwwwaansorgeducationjournalneurosurgicalfeb0314-2-3pdf on February 2003
In order to corroborate the observations at that time with a short follow-up of the open trial the double-blind a placebo-controlled study was initiated in October 2000 the dose of chloroquine for the blind study was decided to be maintained in 150 mg daily for one year after the beginning of therapy
The Research Committee was notified on the beginning and the design of this trial 6000 tablets of chloroquine 150 mg Aralen and 6000 identical tablets of placebo were commercially purchased and sent to the laboratory of Dr Roberto Medina at the National Polytechnic Institute selected as monitor 30 sets of 375 tablets each were separated 15 contained chloroquine and 15 placebo in identical flasks the assignment of treatments was randomly allocated the codified treatments numbered 1-30 were then sent back to our Institute The code was sealed and kept by the monitor until the end of the study Patients included in the study were given the corresponding treatment in sequential order
Criteria for inclusion of patients in the trial is detailed in methods of the manuscript submitted to the Annals of Internal Medicine Ms M0-1087 pages 6-7
Follow-up and statistical analysis End-point evaluation was settled as time of death after the beginning of therapy Follow-up for survivors was settled at 2 years after the beginning of treatment Survival distributions were analyzed as a Kaplan-Meier plot and compared by the log rank test Statistical analysis of demographic clinical and imaging characteristics of patients was made by the t test for independent values
After more than four years from the beginning of the study 26 patients from the originally decided goal number of 30 patients had completed at least two years of follow-up At this time January 2005 it was decided to open the code and proceed with the analysis of those patients which turned out to be 13 chloroquine-treated and 13 placebo-treated patients The last 4 patients who were not included in the analysis are currently under treatment but their follow-up will end next year 2 patients are received chloroquine and the other 2 placebo
No patient initially selected refuse to enter the study nor any patient included was lost at follow-up All 26 patients included in the study have been followed until the time of death or up to July 2005 in survivors
The present protocol started with a controlled open-label clinical trial on 7 patients with GBM and 7 contemporary control patients All patients received the same treatment of extensive surgery carmustine therapy and irradiation at the standard doses as as described in our previous report Surgical Neurology 2000 53157-162 Once selected to enter the study the patients were allocated alternatively in the chloroquine or the control group Endpoint evaluation was settled as surviving time after the beginning of therapy and the end point follow-up was settled in survivors at two years after the beginning of treatment
18 months after the beginning of the open trial it was observed that chloroquine treated patients had a longer survival and no adverse effects to chloroquine therapy were seen
At that time it was decided to start the second part of the protocol designed as a double-blind placebo-controlled trial ideal number of patients to be included was settled in 15 patients on each group
The results of the 1st phase of the study by the open-label trial were published in Neurosurgical Focus httpwwwaansorgeducationjournalneurosurgicalfeb0314-2-3pdf on February 2003
In order to corroborate the observations at that time with a short follow-up of the open trial the double-blind a placebo-controlled study was initiated in October 2000 the dose of chloroquine for the blind study was decided to be maintained in 150 mg daily for one year after the beginning of therapy
The Research Committee was notified on the beginning and the design of this trial 6000 tablets of chloroquine 150 mg Aralen and 6000 identical tablets of placebo were commercially purchased and sent to the laboratory of Dr Roberto Medina at the National Polytechnic Institute selected as monitor 30 sets of 375 tablets each were separated 15 contained chloroquine and 15 placebo in identical flasks the assignment of treatments was randomly allocated the codified treatments numbered 1-30 were then sent back to our Institute The code was sealed and kept by the monitor until the end of the study Patients included in the study were given the corresponding treatment in sequential order
Criteria for inclusion of patients in the trial is detailed in methods of the manuscript submitted to the Annals of Internal Medicine Ms M0-1087 pages 6-7
Follow-up and statistical analysis End-point evaluation was settled as time of death after the beginning of therapy Follow-up for survivors was settled at 2 years after the beginning of treatment Survival distributions were analyzed as a Kaplan-Meier plot and compared by the log rank test Statistical analysis of demographic clinical and imaging characteristics of patients was made by the t test for independent values
After more than four years from the beginning of the study 26 patients from the originally decided goal number of 30 patients had completed at least two years of follow-up At this time January 2005 it was decided to open the code and proceed with the analysis of those patients which turned out to be 13 chloroquine-treated and 13 placebo-treated patients The last 4 patients who were not included in the analysis are currently under treatment but their follow-up will end next year 2 patients are received chloroquine and the other 2 placebo
No patient initially selected refuse to enter the study nor any patient included was lost at follow-up All 26 patients included in the study have been followed until the time of death or up to July 2005 in survivors
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None