CClinicalTrials.gg
Sign In
TerminatedNCT02684071Updated Jan 10, 2020

Phase II Study of Intraventricular Methotrexate in Children With Recurrent or Progressive Malignant Brain Tumors

A Phase 2 interventional study of Intra thecal methotrexate and topotecan in Recurrent Childhood Medulloblastoma, Recurrent Childhood Ependymoma and Childhood Atypical Teratoid/Rhabdoid Tumor, sponsored by Nicklaus Children's Hospital f/k/a Miami Children's Hospital. Terminated at 1 site in United States. Open to participants aged Up to 22 Years. Per ClinicalTrials.gov, last updated 2020-01-10.

Sponsored by Nicklaus Children's Hospital f/k/a Miami Children's Hospital · Phase 2, Interventional, and Treatment

Why this study was terminated
Lack of additional funding; patients (3) no longer receiving intervention.
Phase
Phase 2
Study type
Interventional
Enrollment
3
Allocation
Not applicable
Ages
Up to 22 Years
Sex
All
01

Study summary

The purpose of this research study is to test an experimental treatment method for recurrent or progressive brain tumors in children aged from 0-22 years. The use of methotrexate and chemotherapy (topotecan and cyclophosphamide) is experimental in this study. This means that their use by themselves or together has not been approved by the U.S. Food and Drug Administration for this usage.

Read the detailed description

The purpose of this research study is to test an experimental treatment method for recurrent or progressive brain tumors in children aged from 0-22 years. The use of methotrexate and chemotherapy (topotecan and cyclophosphamide) is experimental in this study. This means that their use by themselves or together has not been approved by the U.S. Food and Drug Administration for this usage. This study will attempt to determine via serial MRI scans if methotrexate administration into the lateral or fourth ventricle in combination with systemic intravenous topotecan and cyclophosphamide is effective in reducing tumor burden in the brain and spine for patients with recurrent or progressive brain tumors, including medulloblastoma, ependymoma, PNET (Primitive Neuroectodermal Tumor), atypical teratoid/rhabdoid tumor (AT/RT), and other malignant embryonal tumors. In addition, the study will evaluate the toxicity of the above mentioned experimental treatment during a two-year progression-free survival and survival of children with recurrent malignant brain tumors.

02

Conditions studied

  • Recurrent Childhood Medulloblastoma
  • Recurrent Childhood Ependymoma
  • Childhood Atypical Teratoid/Rhabdoid Tumor
  • Embryonal Tumor With Abundant Neuropil and True Rosettes
  • Metastatic Malignant Neoplasm to the Leptomeninges

Keywords

  • medulloblastoma, ependymoma, AT/RT, embryonal
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 3 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

Nicklaus Children's Hospital f/k/a Miami Children's Hospital is the lead sponsor of 12 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 22 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Recurrent or progressive supratentorial or posterior fossa tumors with measurable disease on imaging studies of the brain and spine or CSF cytology.
  • Tumor histology, including: Medulloblastoma , PNET, or other embryonal tumor, Atypical teratoid/rhaboid tumor (AT/RT), and Ependymoma.
  • Leptomeningeal dissemination of a previously diagnosed CNS tumor.
  • Diagnosis of tumor pathology will be based upon pathology diagnosis from previous surgeries for patients with recurrent tumors.
  • Patients must have received prior radiation before current recurrence, unless the patient is less than 36 months old at diagnosis and has progressed after at least one upfront chemotherapy regimen in which case no prior radiation is required.
  • Patients must have a life expectancy of at least 12 weeks as indicated by the patient's oncologist and/or neurosurgeon.
  • Lansky or Karnofsky Performance status of at least 50.
  • Negative pregnancy test.
  • Specific organ function requirements for: Central Nervous System, Bone Marrow, renal and liver.

Exclusion criteria

Exclusion Criteria:

  • Patients that do not meet the inclusion criteria above.
  • Pregnant or lactating female patients.
  • Patients currently enrolled in another experimental treatment protocol.
  • Patients with documented allergies to any of the chemotherapy agents used in this study.
  • Patient/Parent refuses study participation.
  • Patient is severely somnolent or comatose.
  • Unable or unwilling to commit to return or to follow-up visits.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
3 participants (actual)

Study arms

  • Experimental
    Intra thecal methotrexate

    IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide

    Drug: Intra thecal methotrexate · Drug: topotecan · Drug: cyclophosphamide

Interventions

  • DrugIntra thecal methotrexate

    IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide

    Also known as: Intra thecal methotrexate, topotecan and cyclophosphamide

  • Drugtopotecan

    To be administered in conjunction with methotrexate

    Also known as: Intra thecal methotrexate, topotecan and cyclophosphamide

  • Drugcyclophosphamide

    To be administered in conjunction with methotrexate and topotecan

    Also known as: Intra thecal methotrexate, topotecan and cyclophosphamide

06

What researchers measure

Primary outcomes

  1. Tumor response

    MRI response

    Time frame: 6 months

Secondary outcomes

  1. Toxicity of chemotherapy regimen (topotecan and cyclophosphamide)

    Laboratory results, MRI, physical examination

    Time frame: 6 months

07

Study locations

1 site
  • Nicklaus Children's Hospital
    Miami, Florida 33155, United States
08

References and documents

Publications

  • Gururangan S, Petros WP, Poussaint TY, Hancock ML, Phillips PC, Friedman HS, Bomgaars L, Blaney SM, Kun LE, Boyett JM. Phase I trial of intrathecal spartaject busulfan in children with neoplastic meningitis: a Pediatric Brain Tumor Consortium Study (PBTC-004). Clin Cancer Res. 2006 Mar 1;12(5):1540-6. doi: 10.1158/1078-0432.CCR-05-2094. PubMed 16533779 ↗
  • Slavc I, Schuller E, Czech T, Hainfellner JA, Seidl R, Dieckmann K. Intrathecal mafosfamide therapy for pediatric brain tumors with meningeal dissemination. J Neurooncol. 1998 Jun-Jul;38(2-3):213-8. doi: 10.1023/a:1005940405165. PubMed 9696374 ↗
  • Yoshimura J, Nishiyama K, Mori H, Takahashi H, Fujii Y. Intrathecal chemotherapy for refractory disseminated medulloblastoma. Childs Nerv Syst. 2008 May;24(5):581-5. doi: 10.1007/s00381-007-0538-8. Epub 2007 Dec 5. PubMed 18057943 ↗
  • Sandberg DI, Solano J, Petito CK, Mian A, Mou C, Koru-Sengul T, Gonzalez-Brito M, Padgett KR, Luqman A, Buitrago JC, Alam F, Wilkerson JR, Crandall KM, Kuluz JW. Safety and pharmacokinetic analysis of methotrexate administered directly into the fourth ventricle in a piglet model. J Neurooncol. 2010 Dec;100(3):397-406. doi: 10.1007/s11060-010-0210-0. Epub 2010 May 4. PubMed 20440538 ↗
  • Sandberg DI, Crandall KM, Koru-Sengul T, Padgett KR, Landrum J, Babino D, Petito CK, Solano J, Gonzalez-Brito M, Kuluz JW. Pharmacokinetic analysis of etoposide distribution after administration directly into the fourth ventricle in a piglet model. J Neurooncol. 2010 Mar;97(1):25-32. doi: 10.1007/s11060-009-9998-x. Epub 2009 Aug 18. PubMed 19688296 ↗
  • Sandberg DI, Crandall KM, Petito CK, Padgett KR, Landrum J, Babino D, He D, Solano J, Gonzalez-Brito M, Kuluz JW. Chemotherapy administration directly into the fourth ventricle in a new piglet model. Laboratory Investigation. J Neurosurg Pediatr. 2008 May;1(5):373-80. doi: 10.3171/PED/2008/1/5/373. PubMed 18447671 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 10, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02684071
Lead sponsor
Nicklaus Children's Hospital f/k/a Miami Children's Hospital
Responsible party
Ziad Khatib (Director of Neuro-Oncology, Nicklaus Children's Hospital f/k/a Miami Children's Hospital) — Principal investigator
First posted
Feb 17, 2016
Start date
Feb 2016
Primary completion
Dec 9, 2019
Completion
Dec 9, 2019
Last update
Jan 10, 2020

Study contacts

Ziad Khatib, MD
principal investigator · Nicklaus Children's Hospital

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Jan 2020. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Neoplasms→

Other studies from this sponsor

Nicklaus Children's Hospital f/k/a Miami Children's Hospital

Start the discussion