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

• Status: Recruiting
• Trial end date: 2025-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Treatments: DMP 777; Mebendazole; Piperazine; Piperazine citrate

Criteria

Inclusion Criteria:

1. Patients must have a confirmed recurrent/progressive brain malignancy that have failed at least one prior treatment regimen.

2. Age for inclusion in this trial at time of patient enrollment is ≥ 1 year, and up to 21 years (prior to the 22nd birthday) with any of the recurrent medulloblastoma or recurrent high grade glioma may be consented and treated under this protocol. Patients who turn 22 during the course of the trial will continue to be treated.

3. Karnofsky Performance Score (KPS) > 50% for patients ≥10 years of age. Lansky score of ≥ 50 for children < 10 years of age.

4. Life expectancy greater than 10 weeks.

5. 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

6. 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.

7. 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.

8. For the patient or parent/legal guardian to be able to comply with treatment plan, study procedures and follow-up examinations.

9. Failed any previous front line standard of care therapy that is currently used for the patient's initial diagnosis.

10. Ability to swallow pills, or liquid formulation and for patient or parent/legal guardian to keep an accurate medication record.

Exclusion Criteria:

1. Patients who have known allergy to mebendazole.

2 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.

3 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.

4 Patients who have previously taken mebendazole as part of any experimental anti-cancer protocol, and have failed this therapy.

5 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.

6 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.

7 Patients with human immunodeficiency virus (HIV), hepatitis B surface antigen or hepatitis C positive; or with a history of chronic active hepatitis or cirrhosis.

8 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.

9 Patients who are not available for follow-up assessments or unable to comply with study requirements.