Pilomyxoid AstrocytomaPhase 1/2NCT01837862
A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas
A Phase 1/2 study testing Mebendazole, Vincristine and Carboplatin in people with Pilomyxoid Astrocytoma and Pilocytic Astrocytoma, run by Julie Krystal at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Pilomyxoid Astrocytoma, Pilocytic Astrocytoma, Glioma, Astrocytic
- What is being tested?
- Mebendazole, Vincristine and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Oct 2013to Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age > 1 year of age and ≤ 21 years of age
- Diagnosis
- 2.1. Group A - Low-grade Glioma Group:
- Histology: Biopsy-proven:
- Pilocytic Astrocytoma
- Fibrillary Astrocytoma
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- 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.
- 2.2 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.
Who cannot join
- Age < 1 year or > 21 years
- Patients who have known allergy to mebendazole or benzimidazole class drugs.
- Patients who have previously had a severe side effect, such as agranulocytosis and neutropenia, in conjunction with previous mebendazole or benzimidazole class drug for a parasitic infection .
- 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.
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- 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 after the completion of therapy.
- Patients who are unable to take oral medications because of significant vomiting will be excluded.
- Group A - Low-grade Glioma Group ONLY:
- Patients who have failed prior chemotherapy with vincristine, carboplatin, or temozolomide for this tumor are 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 excluded.
- Patients who progressed on or within 12 weeks after completion of radiotherapy are excluded.
- Patients with a history or current condition that would preclude the use of bevacizumab
Trial locations and contacts
1 site in 1 country.
United States1 site
Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
About this study
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.
Read more
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
Read the detailed description
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.
- Conditions
- Pilomyxoid Astrocytoma, Pilocytic Astrocytoma, Glioma, Astrocytic, Optic Nerve Glioma, Pleomorphic Xanthoastrocytoma, Glioblastoma Multiforme
- Being tested
- Mebendazole, Vincristine, Carboplatin, Temozolomide, Bevacizumab
- Keywords
- pilomyxoid astrocytoma, Pilocytic Astrocytoma, Glioma, Optic Nerve Glioma, mebendazole, Pleomorphic Xanthoastrocytoma, glioblastoma multiforme, anaplastic astrocytoma, gliosarcoma, diffuse intrinsic pontine glioma, DIPG, low-grade glioma, high-grade glioma, brainstem glioma, pediatric
- Medical subject headings
- Astrocytoma, Optic Nerve Glioma, Glioblastoma, Gliosarcoma, Diffuse Intrinsic Pontine Glioma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MebendazoleDrug
Also called Vermox
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).
VincristineDrug
Also called Oncovin
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.
CarboplatinDrug
Also called Paraplatin
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.
TemozolomideDrug
Also called Temodar
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.
BevacizumabDrug
Also called Avastin
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.
IrinotecanDrug
Also called CPT-11, Camptosar
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 group | Role | What they receive |
|---|---|---|
| Low-grade Glioma | Experimental | Patients on the low-grade arm will receive treatment with seven 10-week cycles of carboplatin, vincristine, temozolomide, and mebendazole. Receives: Drug: Mebendazole; Drug: Vincristine; Drug: Carboplatin; Drug: Temozolomide |
| High-grade Glioma/Pontine Glioma | Experimental | 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 Receives: Drug: Mebendazole; Drug: Bevacizumab; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximally tolerated dose of mebendazole in combination with vincristine, carboplatin, and temozolomide
Low-grade glioma patients will receive an assigned dose of mebendazole twice daily in combination with vincristine, carboplatin and temozolomide. During a 10 week induction period, patients will be assessed for dose-limiting toxicity that is beyond the expected toxicity from the standard regimen of vincristine, carboplatin, and temozolomide alone. This outcome measure will use a standard 3+3 design to dose-escalate mebendazole in three dose cohorts of 50 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day.
Measured: Assessed after the 10 week Induction cycle
Maximally tolerated dose of mebendazole in combination with bevacizumab and irinotecan.
High-grade glioma/pontine glioma patients will receive an assigned dose of mebendazole twice daily in combination with bevacizumab and irinotecan. During the first three maintenance therapy cycles (12 weeks), patients will be assessed for dose-limiting toxicity that is beyond the expected toxicity from the standard regimen of bevacizumab and irinotecan alone. This outcome measure will use a standard 3+3 design to dose-escalate mebendazole in three dose cohorts of 50 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day.
Measured: Assessed after the first 3 maintenance cycles (12 weeks)
Secondary outcomes (5)
Survival of patients with low-grade gliomas
3-year event-free survival (EFS) and overall survival (OS) of patients with low-grade gliomas treated with carboplatin, vincristine, temozolomide, and mebendazole in combination following surgical resection, to the extent feasible.
Measured: 3-years post-treatment
Survival of patients with high-grade gliomas
3-year event-free survival (EFS) and overall survival (OS) of patients with high-grade gliomas treated with bevacizumab, irinotecan, and mebendazole in combination following surgical resection to the extent feasible and local irradiation.
Measured: 3-years post-treatment
Frequency of cerebrospinal fluid (CSF) dissemination in pilomyxoid astrocytoma
The frequency of tumor dissemination in the CSF of patients with pilomyxoid astrocytomas treated with carboplatin, vincristine, temozolomide, and mebendazole.
Measured: 3 years post-treatment
Partial or complete response rate on MRI of patients with high-grade gliomas/pontine gliomas
The percentage of patients demonstrating a partial (greater than 50% decrease in tumor volume in 3 dimensions) or complete response on MRI in patients with high-grade gliomas treated with mebendazole in combination with bevacizumab and irinotecan, after surgical resection, to the extent feasible and local irradiation.
Measured: 3-years post-treatment
Partial or complete response rate on MRI of patients with low-grade gliomas
The percentage of patients demonstrating a partial (greater than 50% decrease in tumor volume in 3 dimensions) or complete response on MRI in patients with low-grade gliomas treated with mebendazole in combination with vincristine, carboplatin and temozolomide after surgical resection, to the extent feasible.
Measured: 3-years post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2013 (estimated)
- Study start22 Oct 2013
- Primary completionMar 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (42)Papers the sponsor has linked to this study.
- Other trials for Pilomyxoid AstrocytomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Julie Krystal
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Pharmaceuticals
- Responsible party
- Sponsor-investigator, Julie Krystal, Northwell Health
- Investigators
- Julie Krystal, MD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01837862
- Sponsor's protocol ID
- CCMC1411
- Status last verified
- Aug 2026
- First submitted
- 16 Apr 2013
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tihan T, Fisher PG, Kepner JL, Godfraind C, McComb RD, Goldthwaite PT, Burger PC. Pediatric astrocytomas with monomorphous pilomyxoid features and a less favorable outcome. J Neuropathol Exp Neurol. 1999 Oct;58(10):1061-8. doi: 10.1097/00005072-199910000-00004.
PubMed 10515229Komotar RJ, Mocco J, Jones JE, Zacharia BE, Tihan T, Feldstein NA, Anderson RC. Pilomyxoid astrocytoma: diagnosis, prognosis, and management. Neurosurg Focus. 2005 Jun 15;18(6A):E7.
PubMed 16048293Paraskevopoulos D, Patsalas I, Karkavelas G, Foroglou N, Magras I, Selviaridis P. Pilomyxoid astrocytoma of the cervical spinal cord in a child with rapid progression into glioblastoma: case report and literature review. Childs Nerv Syst. 2011 Feb;27(2):313-21. doi: 10.1007/s00381-010-1171-5. Epub 2010 May 12.
PubMed 20461521Komotar RJ, Carson BS, Rao C, Chaffee S, Goldthwaite PT, Tihan T. Pilomyxoid astrocytoma of the spinal cord: report of three cases. Neurosurgery. 2005;56(1):191. doi: 10.1227/01.NEU.0000146212.95421.B3.
PubMed 15617606Bauman G, Lote K, Larson D, Stalpers L, Leighton C, Fisher B, Wara W, MacDonald D, Stitt L, Cairncross JG. Pretreatment factors predict overall survival for patients with low-grade glioma: a recursive partitioning analysis. Int J Radiat Oncol Biol Phys. 1999 Nov 1;45(4):923-9. doi: 10.1016/s0360-3016(99)00284-9.
PubMed 10571199Desai KI, Nadkarni TD, Muzumdar DP, Goel A. Prognostic factors for cerebellar astrocytomas in children: a study of 102 cases. Pediatr Neurosurg. 2001 Dec;35(6):311-7. doi: 10.1159/000050443.
PubMed 11786699Gajjar A, Sanford RA, Heideman R, Jenkins JJ, Walter A, Li Y, Langston JW, Muhlbauer M, Boyett JM, Kun LE. Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital. J Clin Oncol. 1997 Aug;15(8):2792-9. doi: 10.1200/JCO.1997.15.8.2792.
PubMed 9256121Wisoff JH, Boyett JM, Berger MS, Brant C, Li H, Yates AJ, McGuire-Cullen P, Turski PA, Sutton LN, Allen JC, Packer RJ, Finlay JL. Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children's Cancer Group trial no. CCG-945. J Neurosurg. 1998 Jul;89(1):52-9. doi: 10.3171/jns.1998.89.1.0052.
PubMed 9647172Finlay JL, Wisoff JH. The impact of extent of resection in the management of malignant gliomas of childhood. Childs Nerv Syst. 1999 Nov;15(11-12):786-8. doi: 10.1007/s003810050471.
PubMed 10603023Pollack IF, Claassen D, al-Shboul Q, Janosky JE, Deutsch M. Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases. J Neurosurg. 1995 Apr;82(4):536-47. doi: 10.3171/jns.1995.82.4.0536.
PubMed 7897512Packer RJ, Ater J, Allen J, Phillips P, Geyer R, Nicholson HS, Jakacki R, Kurczynski E, Needle M, Finlay J, Reaman G, Boyett JM. Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg. 1997 May;86(5):747-54. doi: 10.3171/jns.1997.86.5.0747.
PubMed 9126887Conway PD, Oechler HW, Kun LE, Murray KJ. Importance of histologic condition and treatment of pediatric cerebellar astrocytoma. Cancer. 1991 Jun 1;67(11):2772-5. doi: 10.1002/1097-0142(19910601)67:113.0.co;2-#.
PubMed 1851047Fisher BJ, Leighton CC, Vujovic O, Macdonald DR, Stitt L. Results of a policy of surveillance alone after surgical management of pediatric low grade gliomas. Int J Radiat Oncol Biol Phys. 2001 Nov 1;51(3):704-10. doi: 10.1016/s0360-3016(01)01705-9.
PubMed 11597812Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, Sanford RA, Mulhern RK, James HE, Freeman CR, et al. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 1993 Jun 17;328(24):1725-31. doi: 10.1056/NEJM199306173282401.
PubMed 8388548Brown MT, Friedman HS, Oakes WJ, Boyko OB, Hockenberger B, Schold SC Jr. Chemotherapy for pilocytic astrocytomas. Cancer. 1993 May 15;71(10):3165-72. doi: 10.1002/1097-0142(19930515)71:103.0.co;2-n.
PubMed 8490847
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas
- ClinicalTrials.gov ID
- NCT01837862
- Acronym / sponsor ID
- CCMC1411
- Conditions
- Pilomyxoid Astrocytoma, Pilocytic Astrocytoma, Glioma, Astrocytic, Optic Nerve Glioma, Pleomorphic Xanthoastrocytoma, Glioblastoma Multiforme
- Keywords
- pilomyxoid astrocytoma, Pilocytic Astrocytoma, Glioma, Optic Nerve Glioma, mebendazole, Pleomorphic Xanthoastrocytoma, glioblastoma multiforme, anaplastic astrocytoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Julie KrystalUniversity, hospital or other
- Collaborators
- Janssen Pharmaceuticals
- Study start
- 22 Oct 2013 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 23 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low-grade Glioma | Experimental | Drug: Mebendazole, Drug: Vincristine, Drug: Carboplatin, Drug: TemozolomidePatients on the low-grade arm will receive treatment with seven 10-week cycles of carboplatin, vincristine, temozolomide, and mebendazole. |
| High-grade Glioma/Pontine Glioma | Experimental | Drug: Mebendazole, Drug: Bevacizumab, Drug: IrinotecanPatients 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 |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (27 listed)
- Age > 1 year of age and ≤ 21 years of age
- Diagnosis
- 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.
- Histology: Biopsy-proven
Key exclusion criteria (15 listed)
- Age < 1 year or > 21 years
- Patients who have known allergy to mebendazole or benzimidazole class drugs.
- Patients who have previously had a severe side effect, such as agranulocytosis and neutropenia, in conjunction with previous mebendazole or benzimidazole class drug for a parasitic infection .
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MebendazoleAlso: VermoxMebendazole 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). | Drug | High-grade Glioma/Pontine Glioma, Low-grade Glioma |
| VincristineAlso: OncovinLow-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. | Drug | Low-grade Glioma |
| CarboplatinAlso: ParaplatinLow-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. | Drug | Low-grade Glioma |
| TemozolomideAlso: TemodarLow-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. | Drug | Low-grade Glioma |
| BevacizumabAlso: AvastinHigh-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. | Drug | High-grade Glioma/Pontine Glioma |
| IrinotecanAlso: CPT-11, CamptosarHigh-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. | Drug | High-grade Glioma/Pontine Glioma |
Primary outcome
Maximally tolerated dose of mebendazole in combination with vincristine, carboplatin, and temozolomide
Time frame: Assessed after the 10 week Induction cycle
Low-grade glioma patients will receive an assigned dose of mebendazole twice daily in combination with vincristine, carboplatin and temozolomide. During a 10 week induction period, patients will be assessed for dose-limiting toxicity that is beyond the expected toxicity from the standard regimen of vincristine, carboplatin, and temozolomide alone. This outcome measure will use a standard 3+3 design to dose-escalate mebendazole in three dose cohorts of 50 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day.
Maximally tolerated dose of mebendazole in combination with bevacizumab and irinotecan.
Time frame: Assessed after the first 3 maintenance cycles (12 weeks)
High-grade glioma/pontine glioma patients will receive an assigned dose of mebendazole twice daily in combination with bevacizumab and irinotecan. During the first three maintenance therapy cycles (12 weeks), patients will be assessed for dose-limiting toxicity that is beyond the expected toxicity from the standard regimen of bevacizumab and irinotecan alone. This outcome measure will use a standard 3+3 design to dose-escalate mebendazole in three dose cohorts of 50 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day.
5 secondary outcomes
Survival of patients with low-grade gliomas
Time frame: 3-years post-treatment
Survival of patients with high-grade gliomas
Time frame: 3-years post-treatment
Frequency of cerebrospinal fluid (CSF) dissemination in pilomyxoid astrocytoma
Time frame: 3 years post-treatment
Partial or complete response rate on MRI of patients with high-grade gliomas/pontine gliomas
Time frame: 3-years post-treatment
Partial or complete response rate on MRI of patients with low-grade gliomas
Time frame: 3-years post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Background: PubMed 10515229Tihan T, Fisher PG, Kepner JL, Godfraind C, McComb RD, Goldthwaite PT, Burger PC. Pediatric astrocytomas with monomorphous pilomyxoid features and a less favorable outcome. J Neuropathol Exp Neurol. 1999 Oct;58(10):1061-8. doi: 10.1097/00005072-199910000-00004.
- Background: PubMed 16048293Komotar RJ, Mocco J, Jones JE, Zacharia BE, Tihan T, Feldstein NA, Anderson RC. Pilomyxoid astrocytoma: diagnosis, prognosis, and management. Neurosurg Focus. 2005 Jun 15;18(6A):E7.
- Background: PubMed 20461521Paraskevopoulos D, Patsalas I, Karkavelas G, Foroglou N, Magras I, Selviaridis P. Pilomyxoid astrocytoma of the cervical spinal cord in a child with rapid progression into glioblastoma: case report and literature review. Childs Nerv Syst. 2011 Feb;27(2):313-21. doi: 10.1007/s00381-010-1171-5. Epub 2010 May 12.
- Background: PubMed 15617606Komotar RJ, Carson BS, Rao C, Chaffee S, Goldthwaite PT, Tihan T. Pilomyxoid astrocytoma of the spinal cord: report of three cases. Neurosurgery. 2005;56(1):191. doi: 10.1227/01.NEU.0000146212.95421.B3.
- Background: PubMed 10571199Bauman G, Lote K, Larson D, Stalpers L, Leighton C, Fisher B, Wara W, MacDonald D, Stitt L, Cairncross JG. Pretreatment factors predict overall survival for patients with low-grade glioma: a recursive partitioning analysis. Int J Radiat Oncol Biol Phys. 1999 Nov 1;45(4):923-9. doi: 10.1016/s0360-3016(99)00284-9.
- Background: PubMed 11786699Desai KI, Nadkarni TD, Muzumdar DP, Goel A. Prognostic factors for cerebellar astrocytomas in children: a study of 102 cases. Pediatr Neurosurg. 2001 Dec;35(6):311-7. doi: 10.1159/000050443.
- Background: PubMed 9256121Gajjar A, Sanford RA, Heideman R, Jenkins JJ, Walter A, Li Y, Langston JW, Muhlbauer M, Boyett JM, Kun LE. Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital. J Clin Oncol. 1997 Aug;15(8):2792-9. doi: 10.1200/JCO.1997.15.8.2792.
- Background: PubMed 9647172Wisoff JH, Boyett JM, Berger MS, Brant C, Li H, Yates AJ, McGuire-Cullen P, Turski PA, Sutton LN, Allen JC, Packer RJ, Finlay JL. Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children's Cancer Group trial no. CCG-945. J Neurosurg. 1998 Jul;89(1):52-9. doi: 10.3171/jns.1998.89.1.0052.
- Background: PubMed 10603023Finlay JL, Wisoff JH. The impact of extent of resection in the management of malignant gliomas of childhood. Childs Nerv Syst. 1999 Nov;15(11-12):786-8. doi: 10.1007/s003810050471.
- Background: PubMed 7897512Pollack IF, Claassen D, al-Shboul Q, Janosky JE, Deutsch M. Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases. J Neurosurg. 1995 Apr;82(4):536-47. doi: 10.3171/jns.1995.82.4.0536.
- Background: PubMed 9126887Packer RJ, Ater J, Allen J, Phillips P, Geyer R, Nicholson HS, Jakacki R, Kurczynski E, Needle M, Finlay J, Reaman G, Boyett JM. Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg. 1997 May;86(5):747-54. doi: 10.3171/jns.1997.86.5.0747.
- Background: PubMed 1851047Conway PD, Oechler HW, Kun LE, Murray KJ. Importance of histologic condition and treatment of pediatric cerebellar astrocytoma. Cancer. 1991 Jun 1;67(11):2772-5. doi: 10.1002/1097-0142(19910601)67:113.0.co;2-#.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julie Krystal, MD principal investigator
Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mebendazole, Vincristine and Carboplatin in people with Pilomyxoid Astrocytoma and Pilocytic Astrocytoma, run by Julie Krystal at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximally tolerated dose of mebendazole in combination with vincristine, carboplatin, and temozolomide (time frame: Assessed after the 10 week Induction cycle). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01837862, which also lists 42 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.