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

Who is this study for? Child to young adult patients with Astrocytoma
What treatments are being studied? Mebendazole
Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

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

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1
Maximum Age: 21
Healthy Volunteers: No
View:

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

⁃ Diagnosis

• 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

⁃ Gliosarcoma.

⁃ 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 7 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 applicable)

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

Locations
United States
New York
Cohen Children's Medical Center of New York
Recruiting
New Hyde Park
Contact Information
Primary
Julie Krystal, MD
Jkrystal12@northwell.edu
718-470-3460
Backup
Derek R Hanson, MD
DHanson@hackensackumc.org
551-996-5437
Time Frame
Start Date: October 22, 2013
Estimated Completion Date: April 2025
Participants
Target number of participants: 36
Treatments
Experimental: Low-grade Glioma
Patients on the low-grade arm will receive treatment with seven 10-week cycles of carboplatin, vincristine, temozolomide, and mebendazole.
Experimental: High-grade Glioma/Pontine Glioma
Patients on the high-grade glioma/pontine glioma arm will receive treatment with twelve 28-day cycles of bevacizumab, irinotecan, and mebendazole.~*High grade arm enrollment complete, no additional spots
Sponsors
Leads: Julie Krystal
Collaborators: Janssen Pharmaceuticals

This content was sourced from clinicaltrials.gov

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