Phase I Study of Mebendazole Therapy for Recurrent/Progressive Pediatric Brain Tumors

NCT02644291 | Completed Phase 1 DMC

• 2 other identifiers: J15211IRB00072999
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This is a safety (Phase 1) trial using mebendazole for recurrent pediatric brain cancers that include medulloblastoma and high grade glioma, that are no longing responding to standard therapies. The drug mebendazole is an oral drug in a chewable 500 mg orange flavored tablet. It is already approved to treat parasitic infections. The purpose of this study is to determine the safety and side effects for increasing doses of mebendazole, followed by the treatment of an additional 12 patients at the best tolerated dose.

Conditions

Medulloblastoma; Astrocytoma, Grade III; Glioblastoma; Anaplastic Astrocytoma; Brain Stem Neoplasms, Malignant; Oligodendroblastoma; Anaplastic Oligodendroglioma; Malignant Glioma

Keywords

medulloblastoma; Diffuse Intrinsic Pontine Glioma (DIPG); high grade glioma; glioblastoma; brain stem malignant glioma

Outcome Measures

Primary Outcomes (1)

• Adverse events attributed to mebendazole for patients enrolled in this study

  cumulative adverse events from mebendazole therapy in pediatric brain cancer patients

  duration of study, approximately two years

Secondary Outcomes (1)

• Overall survival for patients enrolled in this study

  duration of study , approximately two years

Study Arms (1)

mebendazole

EXPERIMENTAL

oral mebendazole as dose escalation (three groups), or l oral mebendazole at maximum dose for extended cohort. Given in 3 divided doses with meals as chewable 500 mg tablets based on calculated patient surface area.

Drug: Mebendazole

Interventions

Mebendazole DRUG

chewable mebendazole tablets that can also be crushed and mixed with food or drink to be taken daily with meals

Also known as: Vermox, Ovex, Pripsen

mebendazole

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must have a confirmed recurrent/progressive brain malignancy that have failed at least one prior treatment regimen.
• Karnofsky Performance Score (KPS) \> 50% for patients ≥10 years of age. Lansky score of ≥ 50 for children \< 10 years of age.
• Life expectancy greater than 10 weeks.
• Patients must have adequate organ and marrow function as defined below:
• Leukocytes ≥ 3,000 cells per microliter
• Absolute Neutrophil Count ≥ 750 cells per microliter
• Platelets ≥ 75,000 cells per microliter
• aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal
• Total Bilirubin \< 1.5 x upper limit of normal
• Creatinine \< 1.5 x upper limit of normal OR
• Creatinine Clearance ≥ 60 mL/min/1.73m2 for patients with creatinine \> 1.5 x upper limit of normal
• The effects of mebendazole on the developing human fetus are unknown. In rats there is evidence of a teratogenic effect, although there is no evidence of adverse effect from women accidently taking mebendazole (at lower doses) during pregnancy. For this reason, women of child-bearing potential should agree to use birth control while taking mebendazole if there is a reasonable risk of pregnancy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability for patient (and if applicable parent or legal guardian) understand and the willingness to sign a written informed consent document, or for a parent or legal guardian to give assent for those cases where a very young patient is unable to understand or sign the consent.
• For the patient or parent/legal guardian to be able to comply with treatment plan, study procedures and follow-up examinations.
• Failed any previous front line standard of care therapy that is currently used for the patient's initial diagnosis.

You may not qualify if:

• \. Patients who have known allergy to mebendazole.
• 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.
• Patients who are taking metronidazole and cannot be safely moved to a different antibiotic greater than 7 days prior to starting mebendazole therapy. Metronidazole and mebendazole in combination have been associated with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in a case report.
• Patients who have previously taken mebendazole as part of any experimental anti-cancer protocol, and have failed this therapy.
• 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.
• Pregnant women are excluded because mebendazole is a Class C agent with the potential for teratogenic effects. Because it is not known if mebendazole is excreted in breast milk, breastfeeding should be discontinued if the mother is treated with mebendazole.
• Patients with human immunodeficiency virus (HIV), hepatitis B surface antigen or hepatitis C positive; or with a history of chronic active hepatitis or cirrhosis.
• 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.
• Patients who are not available for follow-up assessments or unable to comply with study requirements.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (2)

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21231, United States

Location

Related Publications (4)

• Bai RY, Staedtke V, Aprhys CM, Gallia GL, Riggins GJ. Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme. Neuro Oncol. 2011 Sep;13(9):974-82. doi: 10.1093/neuonc/nor077. Epub 2011 Jul 15.

  PMID: 21764822 BACKGROUND

• Bai RY, Staedtke V, Rudin CM, Bunz F, Riggins GJ. Effective treatment of diverse medulloblastoma models with mebendazole and its impact on tumor angiogenesis. Neuro Oncol. 2015 Apr;17(4):545-54. doi: 10.1093/neuonc/nou234. Epub 2014 Sep 24.

  PMID: 25253417 BACKGROUND

• Bai RY, Staedtke V, Wanjiku T, Rudek MA, Joshi A, Gallia GL, Riggins GJ. Brain Penetration and Efficacy of Different Mebendazole Polymorphs in a Mouse Brain Tumor Model. Clin Cancer Res. 2015 Aug 1;21(15):3462-3470. doi: 10.1158/1078-0432.CCR-14-2681. Epub 2015 Apr 10.

  PMID: 25862759 BACKGROUND

• Larsen AR, Bai RY, Chung JH, Borodovsky A, Rudin CM, Riggins GJ, Bunz F. Repurposing the antihelmintic mebendazole as a hedgehog inhibitor. Mol Cancer Ther. 2015 Jan;14(1):3-13. doi: 10.1158/1535-7163.MCT-14-0755-T. Epub 2014 Nov 5.

  PMID: 25376612 BACKGROUND

MeSH Terms

Conditions

Medulloblastoma; Astrocytoma; Glioblastoma; Brain Stem Neoplasms; Oligodendroglioma; Glioma; Diffuse Intrinsic Pontine Glioma

Interventions

Mebendazole; ovex; Piperazine

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperazines; Heterocyclic Compounds, 1-Ring

Study Officials

• Kenneth J Cohen, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2015
• First Posted: December 31, 2015
• Study Start: May 1, 2016
• Primary Completion: June 9, 2022
• Study Completion: June 9, 2022
• Last Updated: June 23, 2022

Record last verified: 2021-09

Locations

US (2)