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Chloroquine for Treatment of Glioblastoma Multiforme

Study Purpose

Chloroquine is a strong lysosomotropic and DNA-intercalating agent in experimental studies (Neurosurgical Focus 14(2): 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Unknown
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 65 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Tumor restricted to one hemisphere of the brain.
  • - Karnofsky scale >7.
  • - Histologically confirmed GBM in first or second recurrence or relapse.
  • - Adequate hematologic, hepatic and renal function.
  • - Karnofsky performance status score ≥ 70% - Life expectancy ≥ 16 weeks.

Exclusion Criteria:

  • - Gastrointestinal dysfunction.
  • - Compromised cardiac function.
- Concurrent severe and /or uncontrolled medical conditions

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00224978
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 3
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

National Institute of Neurology and Neurosurgery, Mexico
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Julio Sotelo, MD
Principal Investigator Affiliation National Institute of Neurology and Neurosurgery of Mexico
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Completed
Countries Mexico
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma Multiforme
Additional Details

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; 49:969-973 (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; 53:157-162). 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 (http://www.aans.org/education/journal/neurosurgical/feb03/14-2-3.pdf) 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: 6,000 tablets of chloroquine 150 mg (Aralen) and 6,000 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.

Contact a Trial Team

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International Sites

Mexico City, Mexico

Status

Address

National Institute of Neurology and Neurosurgery

Mexico City, , 14269