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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01729260
First received: November 13, 2012
Last updated: November 10, 2016
Last verified: November 2016
  Purpose
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.

Condition Intervention Phase
Newly Diagnosed High-Grade Glioma Drug: Mebendazole Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Mebendazole in Newly Diagnosed High-Grade Glioma Patients Receiving Temozolomide

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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.


Enrollment: 24
Study Start Date: November 2012
Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: mebendazole 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01729260

Locations
United States, Maryland
The Johs Hopkins Hospital
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Gary Gallia, MD Johns Hopkins University School of Medicine, Department of Neurosurgery
  More Information

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01729260     History of Changes
Other Study ID Numbers: J1194
NA_00049848 ( Other Identifier: JHMIRB )
Study First Received: November 13, 2012
Last Updated: November 10, 2016

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
Glioblastoma
mebendazole
temozolomide

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Mebendazole
Piperazine
Piperazine citrate
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antinematodal Agents
Anthelmintics
Antiparasitic Agents
Anti-Infective Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on July 21, 2017