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

Recurrent Childhood Ependymoma Clinical Trial

Official title:

A Phase II Study of Intraventricular Methotrexate With Systemic Topotecan and Cyclophosphamide in Children With Recurrent or Progressive Malignant Brain Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02684071
• Other study ID #: NCH-CNS-1601
• Status: Terminated
• Phase: Phase 2
• Start date: February 2016
• Est. completion date: December 9, 2019

Study information

• Verified date: January 2020
• Source: Nicklaus Children's Hospital f/k/a Miami Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: December 9, 2019
• Est. primary completion date: December 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 22 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Intra thecal methotrexate
IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide
• topotecan
To be administered in conjunction with methotrexate
• cyclophosphamide
To be administered in conjunction with methotrexate and topotecan

Locations

Country	Name	City	State
United States	Nicklaus Children's Hospital	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Nicklaus Children's Hospital f/k/a Miami Children's Hospital

Country where clinical trial is conducted

United States, 

References & 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. — View 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. — View 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 — View 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. — View 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. — View 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. Epub 2007 Dec 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor response	MRI response	6 months
Secondary	Toxicity of chemotherapy regimen (topotecan and cyclophosphamide)	Laboratory results, MRI, physical examination	6 months

External Links

•   Nicklaus Children's Hospital Cancer Center