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Mebendazole in Newly Diagnosed High-Grade Glioma Patients Receiving Temozolomide (Mebendazole)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01729260
Recruitment Status : Active, not recruiting
First Posted : November 20, 2012
Last Update Posted : July 15, 2020
Accelerate Brain Cancer Cure
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE November 13, 2012
First Posted Date  ICMJE November 20, 2012
Last Update Posted Date July 15, 2020
Actual Study Start Date  ICMJE April 4, 2013
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2012)
maximum tolerated dose (MTD) of mebendazole [ Time Frame: 8 months ]
To determine the maximum tolerated dose (MTD) of mebendazole in combination with temozolomide (TMZ) given after surgery and the standard radiation and TMZ treatment in patients with newly diagnosed malignant gliomas.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2020)
Overall Survival [ Time Frame: 10 years ]
Overall survival in years.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2012)
estimate progression-free survival [ Time Frame: 18 months ]
To estimate progression-free survival as the preliminary and potential therapeutic activity of mebendazole in patients with malignant gliomas.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: November 13, 2012)
Evaluate the plasma concentrations of mebendazole, correlate mebendazole exposure with toxicity,estimate overall survival and evaluate pain for patients undergo the treatment [ Time Frame: 18 months ]
1)To evaluate the plasma concentrations of mebendazole in patients with relation to dose. 3) To correlate mebendazole exposure with toxicity and progression-free survival. 4) To estimate overall survival. 5) To evaluate pain for patients undergo the treatment of mebendazole + temozolomide
Descriptive Information
Brief Title  ICMJE Mebendazole in Newly Diagnosed High-Grade Glioma Patients Receiving Temozolomide
Official Title  ICMJE Phase I Study of Mebendazole in Newly Diagnosed High-Grade Glioma Patients Receiving Temozolomide
Brief Summary The purpose of this study is to find the highest dose of mebendazole (MBZ) that can be safely given to people with malignant brain tumors in combination with the current standard of care (temozolomide) without causing severe side effects. We also want to find out if MBZ can slow the growth of the brain tumor. The study doctors have found that MBZ is effective against malignant brain tumors in the laboratory and animal models of brain tumors.
Detailed Description

Glioblastoma (GBM) is the most common and aggressive brain cancer, and despite significant advances in treatment the majority of patients die within two years of diagnosis. During routine animal studies we serendipitously observed that fenbendazole, a benzimidazole antihelminthic used for pinworms, prevented tumor engraftment. Subsequent in vitro and in vivo experiments with benzimidazoles identified mebendazole as the drug having the best results in preclinical testing 1. In GBM cell lines, mebendazole displayed cytotoxicity with IC50s ranging from 0.1-0.3 μM. Mebendazole disrupted microtubule formation in GBM cells and it's in vitro activity was correlated with reduced tubulin polymerization. In two orthotopic mouse glioma models, one syngeneic and one xenograft, mebendazole significantly extended average survival up to 63% compared to untreated controls 1.

Mebendazole is an FDA approved antiparasitic agent with a well-established side effect and safety record and was effective in our animal models in dosing schedules that are documented as safe in humans. Therefore, mebendazole is a possible anti-cancer therapeutic with pre-clinical safety and efficacy and provides a promising opportunity for a clinical trial in patients with malignant gliomas.

In addition, a recently published case report case report from the University of Michigan documented successful long term control in metastatic adrenocortical adenocarcinoma using mebendazole 2. Mebendazole was well tolerated at 200 mg/day and used as the sole treatment after the patient failed other chemotherapies.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Newly Diagnosed High-Grade Glioma
Intervention  ICMJE Drug: Mebendazole
The mebendazole will be given by mouth three times every day on a 28 day cycle. it's in the form of 500 mg chewable tablets, to be taken with meals.
Other Name: Brand name: Vermox
Study Arms  ICMJE Experimental: Mebendazole
All study participants will receive study drug; Mebendazole.
Intervention: Drug: Mebendazole
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 10, 2016)
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2012)
Estimated Study Completion Date  ICMJE September 2025
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients must have histologically confirmed newly diagnosed high-grade glioma(WHO Grade III or IV)
  2. Age ≥18 years
  3. Karnofsky Performance Score (KPS) ≥ 60%
  4. Life expectancy greater than 12 weeks
  5. Patients must have adequate organ and marrow function
  6. Completed >80% of the prescribed radiation therapy and concurrent temozolomide according to the Stupp regimen without grade 3 or 4 hematologic toxicity
  7. Patients may have received Gliadel during surgery
  8. Ability to swallow pills and keep medication record
  9. women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation.
  10. Ability to understand and willingness to sign a written informed consent document
  11. Be able to comply with treatment plan, study procedures and follow-up examinations

Exclusion Criteria:

  1. Patients must not have received prior therapy other than standard chemoradiation according to Stupp et al and Gliadel.
  2. Patients may not be receiving any other investigational agents while on study
  3. Patients who have known allergy to mebendazole or benzimidazole
  4. Patients who have previously had a severe side effect, such as agranulocytosis and neutropenia, in conjunction with previous mebendazole or benzimidazole class drug for a parasitic infection
  5. Patients who are taking metronidazole and cannot be safely moved to a different antibiotic greater than 7 days prior to starting mebendazole therapy
  6. Patients who have taken any benzimidazole (ABZ, flubendazole, thiabendazole, fenbendazole, triclabendazole, etc.) within the last 3 months
  7. Patients who are taking any anti-convulsant medication that interferes with the cytochrome P450 pathway (e.g. phenytoin, phenobarbital, carbamazepine, etc.)
  8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, chronic hepatitis, acute hepatitis, or psychiatric illness/social situation that would limit compliance with study requirements
  9. Pregnant women are excluded
  10. Patients with human immunodeficiency virus (HIV), hepatitis B surface antigen or hepatitis C positive; or with a history of chronic active hepatitis or cirrhosis
  11. Patients with a history of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product administration or may interfere with the interpretation of the results
  12. Patients who are not available for follow-up assessments or unable to comply with study requirements
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01729260
Other Study ID Numbers  ICMJE J1194
NA_00049848 ( Other Identifier: JHMIRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE Accelerate Brain Cancer Cure
Investigators  ICMJE
Principal Investigator: Gary Gallia, MD Johns Hopkins University School of Medicine, Department of Neurosurgery
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP