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

NCT02684071 | Terminated Phase 2 DMC

• 1 other identifier: NCH-CNS-1601
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Tumor response

  MRI response

  6 months

Secondary Outcomes (1)

• Toxicity of chemotherapy regimen (topotecan and cyclophosphamide)

  6 months

Study Arms (1)

Intra thecal methotrexate

EXPERIMENTAL

IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide

Drug: Intra thecal methotrexate; Drug: topotecan; Drug: cyclophosphamide

Interventions

Intra thecal methotrexate DRUG

IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide

Also known as: Intra thecal methotrexate, topotecan and cyclophosphamide

Intra thecal methotrexate

topotecan DRUG

To be administered in conjunction with methotrexate

Also known as: Intra thecal methotrexate, topotecan and cyclophosphamide

Intra thecal methotrexate

cyclophosphamide DRUG

To be administered in conjunction with methotrexate and topotecan

Also known as: Intra thecal methotrexate, topotecan and cyclophosphamide

Intra thecal methotrexate

Eligibility Criteria

• Age: Up to 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nicklaus Children's Hospital f/k/a Miami Children's Hospital: lead

Study Sites (1)

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Related Publications (6)

• 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.

  PMID: 16533779 BACKGROUND

• 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.

  PMID: 9696374 BACKGROUND

• 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.

  PMID: 18057943 BACKGROUND

• 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.

  PMID: 20440538 BACKGROUND

• 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.

  PMID: 19688296 BACKGROUND

• 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.

  PMID: 18447671 RESULT

Related Links

• Nicklaus Children's Hospital Cancer Center

MeSH Terms

Conditions

Medulloblastoma; Familial ependymoma; Rhabdoid Tumor; Neuroectodermal Tumors, Primitive; Meningeal Carcinomatosis; Ependymoma

Interventions

Topotecan; Cyclophosphamide

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Ziad Khatib, MD

  Nicklaus Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Neuro-Oncology

Study Record Dates

• First Submitted: February 11, 2016
• First Posted: February 17, 2016
• Study Start: February 1, 2016
• Primary Completion: December 9, 2019
• Study Completion: December 9, 2019
• Last Updated: January 10, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)