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

  • End date
    Apr 1, 2025
  • participants needed
  • sponsor
    Julie Krystal
Updated on 1 May 2022
progressive disease
chemotherapy drug
tumor cells
complete resection
spinal cord
chemotherapy drugs
chemotherapeutic agents
glioblastoma multiforme
malignant glioma
brain tumor
anaplastic astrocytoma
low grade glioma
astrocytoma, anaplastic
pilocytic astrocytoma
brainstem tumor
pilomyxoid astrocytoma
pleomorphic xanthoastrocytoma


This is a study to determine the safety and efficacy of the drug, mebendazole, when used in combination with standard chemotherapy drugs for the treatment of pediatric brain tumors. Mebendazole is a drug used to treat infections with intestinal parasites and has a long track record of safety in humans. Recently, it was discovered that mebendazole may be effective in treating cancer as well, in particular brain tumors. Studies using both cell cultures and mouse models demonstrated that mebendazole was effective in decreasing the growth of brain tumor cells.

This study focuses on the treatment of a category of brain tumors called gliomas. Low-grade gliomas are tumors arising from the glial cells of the central nervous system and are characterized by slower, less aggressive growth than that of high-grade gliomas. Some low-grade gliomas have a more aggressive biology and an increased likelihood of resistance or recurrence.

Low-grade gliomas are often able to be treated by observation alone if they receive a total surgical resection. However, tumors which are only partially resected and continue to grow or cause symptoms, or those which recur following total resection require additional treatment, such as chemotherapy. Due to their more aggressive nature, pilomyxoid astrocytomas, even when totally resected, will often be treated with chemotherapy. The current first-line treatment at our institution for these low-grade gliomas involves a three-drug chemotherapy regimen of vincristine, carboplatin, and temozolomide. However, based on our data from our own historical controls, over 50% of patients with pilomyxoid astrocytomas will continue to have disease progression while on this treatment. We believe that mebendazole in combination with vincristine, carboplatin, and temozolomide may provide an additional therapeutic benefit with increased progression-free and overall survival for low-grade glioma patients, particularly for those with pilomyxoid astrocytomas.

High grade gliomas are more aggressive tumors with poor prognoses. The standard therapy is radiation therapy. A variety of adjuvant chemotherapeutic combinations have been used, but with disappointing results. For high-grade gliomas this study will add mebendazole to the established combination of bevacizumab and irinotecan to determine this combinations safety and efficacy


This is a phase I/II study of mebendazole in combination with standard of care agents for pediatric patients with gliomas. Patients with low-grade gliomas will receive a regimen of mebendazole in combination with vincristine, carboplatin, and temozolomide. Patients with high-grade gliomas and diffuse intrinsic pontine gliomas will receive a regimen of mebendazole in combination with bevacizumab and irinotecan. Surgical resection of the tumor will be attempted initially with the goal of achieving a gross total resection without substantial neurologic deficit. Subtotal resection may be preferable depending on the location of the tumor. Optic pathway gliomas and diffuse intrinsic pontine gliomas may remain unresected. Patients with high-grade gliomas or diffuse intrinsic pontine gliomas will undergo local irradiation of their tumor before beginning protocol treatment. Low-grade glioma patients will not receive radiation therapy. Patients who have been previously treated with chemotherapy will be eligible for the study provided they have not previously failed therapy with any of the chemotherapeutic agents.

Patients with eligible tumors will be consented for enrollment into the study. The study patients will be divided into two groups (low-grade glioma and high-grade/pontine glioma) for the purpose of determining the maximally tolerated dose of mebendazole. These two groups will be treated independently with regard to patient accrual, dose escalation, and evaluation of toxicity. In addition to their standard chemotherapy regimen, patients in both cohorts will receive mebendazole. Mebendazole doses will be escalated from the initial dose level of 50 mg/kg/day divided twice daily, to a second dose level of 100 mg/kg/day divided twice daily, to the final dose level of 200 mg/kg/day divided twice daily, in cohorts of three patients per dose level. A standard "3+3" design will be used for determining dose escalation.

Phase I safety monitoring for the low-grade group will take place during a trial period beginning with start of therapy and ending following the tenth week of induction therapy. Phase I safety monitoring for the high-grade/pontine glioma group will take place during a trial period beginning with the start of maintenance therapy through the twelfth week of maintenance therapy (3 cycles).

After determination of maximally tolerated dose for each group, the study will continue to evaluate efficacy of this regimen. The study will be amended for the maximally tolerated dose for each group to be used in the remainder of the study. Patients currently on study will continue with maintenance therapy. To document the degree of residual tumor, standard whole brain MRI with and without contrast (gadolinium) will be performed following a specified intervals. Following completion of therapy, patients will continue to be monitored by MRI to assess progression-free and overall-survival.

Condition Pilomyxoid Astrocytoma, Pilocytic Astrocytoma, Glioma, Astrocytic, Optic Nerve Glioma, Pleomorphic Xanthoastrocytoma, Glioblastoma Multiforme, Anaplastic Astrocytoma, Gliosarcoma, Diffuse Intrinsic Pontine Glioma, DIPG, Low-grade Glioma, Brainstem Glioma
Treatment carboplatin, bevacizumab, Temozolomide, Irinotecan, vincristine, Mebendazole, Mebendazole
Clinical Study IdentifierNCT01837862
SponsorJulie Krystal
Last Modified on1 May 2022


Yes No Not Sure

Inclusion Criteria

Age > 1 year of age and ≤ 21 years of age
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 MRI
and/or symptoms of deteriorating vision or, progressive hypothalamic/pituitary
dysfunction or, diencephalic syndrome or precocious puberty
Patients with relapsed low-grade gliomas who have been previously treated with
chemotherapy will be eligible for the study provided they have not previously failed
therapy with any of the chemotherapeutic agents used in this study
2 Group B - High-grade Glioma/Pontine Glioma Group
Histology: Biopsy-proven
Anaplastic astrocytoma
Glioblastoma multiforme
Patients with primary spinal cord malignant gliomas are eligible
For primary brainstem tumors, histologic verification is not required. Patients are
eligible when diagnosed with clinical and radiographic (MRI) evidence of tumors which
diffusely involve the brainstem. Patients with tumors which intrinsically (greater
than 50% intra-axial) involve the pons or pons and medulla or pons and midbrain or
entire brainstem are eligible. Tumors may contiguously involve the thalamus or upper
cervical cord
Timing of therapy
Patients must be enrolled before treatment begins. Treatment must start within 14 days
of study enrollment
All clinical and laboratory studies to determine eligibility must be performed within
days prior to enrollment unless otherwise indicated in the eligibility section
Adequate hematologic, renal, liver function as demonstrated by laboratory values
Negative pregnancy test in women of childbearing potential within 7 days of initiating
investigational therapy
Life expectancy ≥ 3 months
Concurrent medications: It is recommended that patients are weaned off or are on a
tapering dose of corticosteroids before starting therapy on study
Patient or legal guardian must give written, informed consent or assent (when
Recent mothers must agree not to breast feed while receiving medications on study

Exclusion Criteria

Patients who have previously had a severe side effect, such as agranulocytosis and
neutropenia, in conjunction with previous mebendazole or benzimidazole class drug for
Age < 1 year or > 21 years
a parasitic infection
Patients who have known allergy to mebendazole or benzimidazole class drugs
Patients who are taking metronidazole and cannot be safely moved to a different
antibiotic greater than 7 days prior to starting mebendazole therapy
Pregnant female patients are not eligible for this study. Pregnancy tests with a
negative result must be obtained in all post-menarchal females
Lactating females must agree they will not breastfeed a child while on this study
Males and females of reproductive potential may not participate unless they agree to
use an effective contraceptive method and continue to do so for at least 6 months
Group A - Low-grade Glioma Group ONLY
after the completion of therapy
Patients who have failed prior chemotherapy with vincristine, carboplatin, or
Patients who are unable to take oral medications because of significant vomiting will
temozolomide for this tumor are excluded
be excluded
Patients with Neurofibromatosis Type 1
Group B - High-grade Glioma/Pontine Glioma Group ONLY
Patients who failed prior chemotherapy with bevacizumab or irinotecan for this tumor are
Patients who progressed on or within 12 weeks after completion of radiotherapy are
Patients with a history or current condition that would preclude the use of bevacizumab
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