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

Part of paid clinical trials in New Hyde Park, New York.

Sponsor
Julie Krystal
Study ID
NCT01837862
Phase
PHASE1/PHASE2
Status
Completed

Conditions

  • Anaplastic Astrocytoma
  • Brainstem Glioma
  • DIPG
  • Diffuse Intrinsic Pontine Glioma
  • Glioblastoma Multiforme
  • Glioma, Astrocytic
  • Gliosarcoma
  • Low-grade Glioma
  • Optic Nerve Glioma
  • Pilocytic Astrocytoma
  • Pilomyxoid Astrocytoma
  • Pleomorphic Xanthoastrocytoma

Eligibility Criteria

Sex
ALL
Age
1 Year - 21 Years
Healthy Volunteers
Not accepted

Interventions

  • Mebendazole — DRUG
    Mebendazole will be given orally twice daily for over the course of treatment (70 weeks for low-grade glioma patients, 48 weeks for high-grade glioma/pontine glioma patients). Mebendazole will be prescribed according to the particular dose cohort for each patient (50 mg/kg/day, 100 mg/kg/day, or 200 mg/kg/day).
  • Vincristine — DRUG
    Low-grade glioma patients only. Vincristine will be dosed as per the following: For patients \< 12kg: 0.05 mg/kg; for patient \> 12kg: 1.5mg/m2 (maximal dose 2.0 mg). Vincristine will be administered intravenously on Day 1 of weeks 0,1,2,3,4,5 during the 10-week induction cycle and on Day 1 of Weeks 0,1,2 of the six 10-week maintenance cycles.
  • Carboplatin — DRUG
    Low-grade glioma patients only. Carboplatin will be dosed at 175 mg/m2. Carboplatin will be administered intravenously on Day 1 of Weeks 0,1,2,3 of the 10-week Induction cycle, and on Day 1 of Weeks 0,1,2,3 during the six 10-week maintenance cycles.
  • Temozolomide — DRUG
    Low-grade glioma patients only. Temozolomide will be dosed at 200 mg/m2/day. Temozolomide will be given orally for 5 days during Week 6 of the 10-week induction cycle and for 5 days during Week 6 of the six 10-week maintenance cycles.
  • Bevacizumab — DRUG
    High-grade glioma/pontine glioma patients only. Bevacizumab will be dosed at 10mg/kg/dose. Bevacizumab will be administered intravenously on Days 1 and 15 of each maintenance cycle.
  • Irinotecan — DRUG
    High-grade glioma/pontine glioma patients only. Irinotecan will be administered at doses 125 mg/m2, 150 mg/m2, 250 mg/m2, or 300 mg/m2, depending on patient tolerance and concomitant enzyme-inducing anti-epileptic medication use. Irinotecan will be administered intravenously on Days 1 and 15 of each maintenance cycle.

Study Details

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

Key Dates

Start date
Oct 22, 2013
Status verified
Jul 2024
Primary completion
Apr 30, 2024
Completion
Apr 30, 2024

Study Design

Enrollment
36 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • 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

Primary Outcome Measure

Maximally tolerated dose of mebendazole in combination with vincristine, carboplatin, and temozolomide [ Time Frame: Assessed after the 10 week Induction cycle ]

Locations (1)

FacilityCityStateZIPSite coordinators
Cohen Children's Medical Center of New YorkNew Hyde ParkNew York11040-

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Cohen Children's Medical Center of New York· New Hyde Park, NY

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