Phase I Study of Mebendazole Therapy for Recurrent/Progressive Pediatric Brain Tumors
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|ClinicalTrials.gov Identifier: NCT02644291|
Recruitment Status : Recruiting
First Posted : December 31, 2015
Last Update Posted : August 15, 2018
|Condition or disease||Intervention/treatment||Phase|
|Medulloblastoma Astrocytoma, Grade III Glioblastoma Anaplastic Astrocytoma Brain Stem Neoplasms, Malignant Oligodendroblastoma Anaplastic Oligodendroglioma Malignant Glioma||Drug: Mebendazole||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Mebendazole Therapy for Recurrent/Progressive Pediatric Brain Tumors|
|Study Start Date :||May 2016|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||June 2021|
oral mebendazole as dose escalation (three groups), or l oral mebendazole at maximum dose for extended cohort. Given in 3 divided doses with meals as chewable 500 mg tablets based on calculated patient surface area.
chewable mebendazole tablets that can also be crushed and mixed with food or drink to be taken daily with meals
- Adverse events attributed to mebendazole for patients enrolled in this study [ Time Frame: duration of study, approximately two years ]cumulative adverse events from mebendazole therapy in pediatric brain cancer patients
- Overall survival for patients enrolled in this study [ Time Frame: duration of study , approximately two years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02644291
|Contact: Tammy Scott, RN||4106145990||SCOTTTA@jhmi.edu|
|Contact: Kenneth J Cohen, MDfirstname.lastname@example.org|
|United States, Florida|
|Johns Hopkins All Children's Hospital||Recruiting|
|Saint Petersburg, Florida, United States, 33701|
|Contact: Stacie Stapleton, M.D. 727-767-4176 email@example.com|
|United States, Maryland|
|Johns Hopkins University School of Medicine||Recruiting|
|Baltimore, Maryland, United States, 21231|
|Contact: Tammy Scott, RN 410-614-5990 SCOTTTA@jhmi.edu|
|Contact: Kenneth J Cohen, MD 410-614-5055 firstname.lastname@example.org|
|Principal Investigator: Kenneth J Cohen, MD|
|Principal Investigator:||Kenneth J Cohen, MD||Johns Hopkins University|