Clinical trial NCT02684071: Phase II Study of Intraventricular Methotrexate in Children With Recurrent or Progressive Malignant Brain Tumors
Official title: A Phase II Study of Intraventricular Methotrexate With Systemic Topotecan and Cyclophosphamide in Children With Recurrent or Progressive Malignant Brain Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Nicklaus Children's Hospital f/k/a Miami Children's Hospital
Sponsor class: OTHER
First posted: 2016-02-17
Enrollment: 3
Sex: ALL
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Tumor response
timeFrame: 6 months
Secondary outcomes:
measure: Toxicity of chemotherapy regimen (topotecan and cyclophosphamide)
timeFrame: 6 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
Study officials:
affiliation: Nicklaus Children's Hospital
name: Ziad Khatib, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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citation: 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.
citation: 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.