A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas

Inclusion Criteria:

1. Age > 1 year of age and ≤ 21 years of age

2. Diagnosis

2.1. Group A - Low-grade Glioma Group: Histology: Biopsy-proven:

• Pilocytic Astrocytoma

• Fibrillary Astrocytoma

• Pilomyxoid Astrocytoma

• Pleomorphic Xanthoastrocytoma

• Other low grade astrocytomas Children with optic pathway tumors must have evidence of progressive disease on MRIand/or symptoms of deteriorating vision or, progressive hypothalamic/pituitarydysfunction or, diencephalic syndrome or precocious puberty. Patients with relapsed low-grade gliomas who have been previously treated withchemotherapy will be eligible for the study provided they have not previously failedtherapy with any of the chemotherapeutic agents used in this study.

2.2 Group B - High-grade Glioma/Pontine Glioma Group: Histology: Biopsy-proven

• Anaplastic astrocytoma

• Glioblastoma multiforme

• Gliosarcoma. Patients with primary spinal cord malignant gliomas are eligible. For primary brainstem tumors, histologic verification is not required. Patients areeligible when diagnosed with clinical and radiographic (MRI) evidence of tumorswhich diffusely involve the brainstem. Patients with tumors which intrinsically (greater than 50% intra-axial) involve the pons or pons and medulla or pons andmidbrain or entire brainstem are eligible. Tumors may contiguously involve thethalamus or upper cervical cord.

3. Timing of therapy: Patients must be enrolled before treatment begins. Treatment must start within 14days of study enrollment. All clinical and laboratory studies to determine eligibility must be performedwithin 7 days prior to enrollment unless otherwise indicated in the eligibilitysection.

4. Adequate hematologic, renal, liver function as demonstrated by laboratory values.

5. Negative pregnancy test in women of childbearing potential within 7 days ofinitiating investigational therapy

6. Life expectancy ≥ 3 months

7. Concurrent medications: It is recommended that patients are weaned off or are on atapering dose of corticosteroids before starting therapy on study.

8. Patient or legal guardian must give written, informed consent or assent (whenapplicable)

9. Recent mothers must agree not to breast feed while receiving medications on study.

Exclusion criteria:

1. Age < 1 year or > 21 years

2. Patients who have known allergy to mebendazole or benzimidazole class drugs.

3. Patients who have previously had a severe side effect, such as agranulocytosis andneutropenia, in conjunction with previous mebendazole or benzimidazole class drugfor a parasitic infection .

4. Patients who are taking metronidazole and cannot be safely moved to a differentantibiotic greater than 7 days prior to starting mebendazole therapy.

5. Pregnant female patients are not eligible for this study. Pregnancy tests with anegative result must be obtained in all post-menarchal females.

6. Lactating females must agree they will not breastfeed a child while on this study.

7. Males and females of reproductive potential may not participate unless they agree touse an effective contraceptive method and continue to do so for at least 6 monthsafter the completion of therapy.

8. Patients who are unable to take oral medications because of significant vomitingwill be excluded.

9. Group A - Low-grade Glioma Group ONLY: Patients who have failed prior chemotherapy with vincristine, carboplatin, ortemozolomide for this tumor are excluded. Patients with Neurofibromatosis Type 1

10. Group B - High-grade Glioma/Pontine Glioma Group ONLY:

Patients who failed prior chemotherapy with bevacizumab or irinotecan for this tumor are excluded.

Patients who progressed on or within 12 weeks after completion of radiotherapy are excluded.

Patients with a history or current condition that would preclude the use of bevacizumab