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

Primary Purpose

Recurrent Childhood Medulloblastoma, Recurrent Childhood Ependymoma, Childhood Atypical Teratoid/Rhabdoid Tumor

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Intra thecal methotrexate

topotecan

cyclophosphamide

About this trial

This is an interventional treatment trial for Recurrent Childhood Medulloblastoma focused on measuring medulloblastoma, ependymoma, AT/RT, embryonal

Eligibility Criteria

undefined - 22 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Nicklaus Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intra thecal methotrexate

Arm Description

IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide

Outcomes

Primary Outcome Measures

Tumor response

MRI response

Secondary Outcome Measures

Toxicity of chemotherapy regimen (topotecan and cyclophosphamide)

Laboratory results, MRI, physical examination

Full Information

NCT ID

NCT02684071

First Posted

February 11, 2016

Last Updated

January 7, 2020

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT02684071

Brief Title

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

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Terminated

Why Stopped

Lack of additional funding; patients (3) no longer receiving intervention.

Study Start Date

February 2016 (Actual)

Primary Completion Date

December 9, 2019 (Actual)

Study Completion Date

December 9, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

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

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intra thecal methotrexate

Arm Type

Experimental

Arm Description

IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide

Intervention Type

Drug

Intervention Name(s)

Intra thecal methotrexate

Other Intervention Name(s)

Intra thecal methotrexate, topotecan and cyclophosphamide

Intervention Description

IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide

Intervention Type

Drug

Intervention Name(s)

topotecan

Other Intervention Name(s)

Intra thecal methotrexate, topotecan and cyclophosphamide

Intervention Description

To be administered in conjunction with methotrexate

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Other Intervention Name(s)

Intra thecal methotrexate, topotecan and cyclophosphamide

Intervention Description

To be administered in conjunction with methotrexate and topotecan

Primary Outcome Measure Information:

Title

Tumor response

Description

MRI response

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Toxicity of chemotherapy regimen (topotecan and cyclophosphamide)

Description

Laboratory results, MRI, physical examination

Time Frame

6 months

10. Eligibility

Sex

All

Maximum Age & Unit of Time

22 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ziad Khatib, MD

Organizational Affiliation

Nicklaus Children's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Nicklaus Children's Hospital

City

Miami

State/Province

Florida

ZIP/Postal Code

33155

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

16533779

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.

Results Reference

background

PubMed Identifier

9696374

Citation

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.

Results Reference

background

PubMed Identifier

18057943

Citation

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.

Results Reference

background

PubMed Identifier

20440538

Citation

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.

Results Reference

background

PubMed Identifier

19688296

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.

Results Reference

background

PubMed Identifier

18447671

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.

Results Reference

result

Links:

URL

https://www.nicklauschildrens.org/medical-services/cancer-center.aspx

Description

Nicklaus Children's Hospital Cancer Center

Learn more about this trial

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

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