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

Inclusion Criteria:

1. Patients must have a confirmed recurrent/progressive brain malignancy that have failedat 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 orrecurrent high grade glioma may be consented and treated under this protocol. Patientswho 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 upperlimit 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 xupper limit of normal

6. The effects of mebendazole on the developing human fetus are unknown. In rats there isevidence of a teratogenic effect, although there is no evidence of adverse effect fromwomen accidently taking mebendazole (at lower doses) during pregnancy. For thisreason, women of child-bearing potential should agree to use birth control whiletaking mebendazole if there is a reasonable risk of pregnancy. Should a woman becomepregnant or suspect she is pregnant while participating in this study, she shouldinform her treating physician immediately.
7. Ability for patient (and if applicable parent or legal guardian) understand and thewillingness to sign a written informed consent document, or for a parent or legalguardian to give assent for those cases where a very young patient is unable tounderstand 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 thepatient's initial diagnosis.
10. Ability to swallow pills, or liquid formulation and for patient or parent/legalguardian 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 andneutropenia, in conjunction with previous mebendazole or benzimidazole class drug for aparasitic infection.

3 Patients who are taking metronidazole and cannot be safely moved to a differentantibiotic greater than 7 days prior to starting mebendazole therapy. Metronidazole andmebendazole in combination have been associated with Stevens-Johnson Syndrome/ToxicEpidermal Necrolysis in a case report.

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

5 Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, uncontrolled hypertension, symptomatic congestive heart failure, unstable anginapectoris, cardiac arrhythmia, chronic hepatitis, acute hepatitis, or psychiatricillness/social situation that would limit compliance with study requirements.

6 Pregnant women are excluded because mebendazole is a Class C agent with the potential forteratogenic 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 orhepatitis 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 abnormalitythat in the opinion of the investigator may increase the risks associated with the studyparticipation or investigational product administration or may interfere with theinterpretation of the results.

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