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

Phase 2

Terminated

• Conditions: Childhood Atypical Teratoid/Rhabdoid Tumor; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Embryonal Tumor With Abundant Neuropil and True Rosettes; Metastatic Malignant Neoplasm to the Leptomeninges
• Interventions: Drug: Intra thecal methotrexate; Drug: topotecan; Drug: cyclophosphamide

• Registration Number: NCT02684071
• Lead Sponsor: Nicklaus Children's Hospital f/k/a Miami Children's Hospital

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.

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.

Study Timeline

• Study Start: 2016-02
• Study First Submitted: 2016-02-11
• Study First Submitted QC: 2016-02-11
• Study First Posted: 2016-02-17
• Primary Completion: 2019-12-09
• Study Completion: 2019-12-09
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-07
• Last Update Posted: 2020-01-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intra thecal methotrexate	Intra thecal methotrexate	IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide
Intra thecal methotrexate	cyclophosphamide	IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide
Intra thecal methotrexate	topotecan	IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide

Primary Outcome Measures

Name	Time	Method
Tumor response	6 months	MRI response

Secondary Outcome Measures

Name	Time	Method
Toxicity of chemotherapy regimen (topotecan and cyclophosphamide)	6 months	Laboratory results, MRI, physical examination

Trial Locations

Locations (1)

Nicklaus Children's Hospital; 🇺🇸 Miami, Florida, United States