Phase I Study of Mebendazole Therapy for Recurrent/Progressive Pediatric Brain Tumors
Condition: Medulloblastoma; Astrocytoma, Grade III; Glioblastoma; Anaplastic Astrocytoma; Brain Stem Neoplasms, Malignant; Oligodendroblastoma; Anaplastic Oligodendroglioma; Malignant Glioma
MeSH terms: Glioblastoma; Glioma; Astrocytoma; Medulloblastoma; Oligodendroglioma; Neoplasms; Brain Stem Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a safety (Phase 1) trial using mebendazole for recurrent pediatric brain cancers that
      include medulloblastoma and high grade glioma, that are no longing responding to standard
      therapies. The drug mebendazole is an oral drug in a chewable 500 mg orange flavored tablet.
      It is already approved to treat parasitic infections. The purpose of this study is to
      determine the safety and side effects for increasing doses of mebendazole, followed by the
      treatment of an additional 12 patients at the best tolerated dose.
    

Detailed description: 
      The primary objectives of this study are to determine the maximum tolerated dose (MTD) of
      oral mebendazole in patients with recurrent/progressive pediatric brain tumors and to confirm
      the tolerance of the MTD of oral mebendazole by assessing tolerance in a dose expansion
      cohort. Secondary Objectives of the study include to determine the safety, tolerability and
      toxicity of mebendazole in this patient population, determine the plasma levels of
      mebendazole in this patient population and Determine progression-free and overall survival of
      mebendazole in an extended cohort of patients with treatment refractory pediatric brain
      cancer.

      Mebendazole (MBZ) is a drug developed to treat human helminthic disease and is FDA-approved
      for the treatment of roundworm, common hookworm, American hookworm, pinworm and whipworm. MBZ
      use is well documented and frequently used in tropical countries at higher doses for the
      rarer parasitic infections of the brain.

      We have shown efficacy in preclinical laboratory models of high grade glioma and
      medulloblastoma. Mebendazole therapy demonstrated safety in a phase I clinical trial for
      adults with high grade gliomas such as glioblastoma. This trial completed the maximum
      approved enrollment of 24 patients treated with mebendazole, with high doses consistent with
      dosing published for severe parasitic infections.

      Laboratory studies indicate that mebendazole enters the brain and brain tumors at
      concentrations that may be effective for a combination of anti-cancer mechanisms. In animal
      models of brain cancer evidence suggest that mebendazole can prevent cell proliferation by
      interfering with tubulin formation, and it may prevent the formation of new abnormal blood
      vessels that feed tumor growth.

      The patients for this experimental trial are those between the age of 1 to 21 with the
      diagnosis of medulloblastoma, or high grade glioma, where the tumor has resumed growth or
      continued to grow despite standard medical therapy. High grade glioma are those with a World
      Health Organization (WHO) grade of III or IV. It includes diagnosis of pediatric
      glioblastoma, anaplastic astrocytoma, and diffuse intrinsic pontine glioma. Patients who have
      failed other forms of experimental therapy may also be eligible for this trial.

      Mebendazole is provided at no cost in the form of a chewable 500 mg tablets, recommended to
      be taken three times daily with meals or food. The pill can be chewed after meals, or ground
      up to be mixed with food or drink. It has a mild orange flavor that is similar in consistency
      to an antacid tablet.

      Although side effects are rare and the vast majority are reversible, they include stomach
      upset, decreased blood count, and elevated liver enzymes due to inflammation.

      The main additional procedure beyond taking this drug, is that patients are requested to
      consent to up to three additional blood draws to check the blood (serum) levels of the drug
      to ensure it is being absorbed at sufficient doses.

      Patients can continue to receive the drug as long as in the attending physicians opinion the
      therapy is not causing any severe side effects, and there is no clear indication that the
      patient will not respond to mebendazole therapy. Patients can withdraw from this trial at any
      time for any reason, and may be eligible for other experimental therapies afterwards.
    

Intervention name(s): Mebendazole
Intervention type(s): Drug
Intervention description(s): chewable mebendazole tablets that can also be crushed and mixed with food or drink to be taken daily with meals
Other intervention name(s): Vermox; Ovex; Pripsen
Intervention MeSH terms: Mebendazole; Piperazine; Piperazine citrate; DMP 777
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: medulloblastoma; Diffuse Intrinsic Pontine Glioma (DIPG); high grade glioma; glioblastoma; brain stem malignant glioma