Recurrent Childhood MedulloblastomaPhase 2NCT02684071

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

A Phase 2 study testing Intra thecal methotrexate, topotecan and cyclophosphamide in people with Recurrent Childhood Medulloblastoma and Recurrent Childhood Ependymoma, run by Nicklaus Children's Hospital f/k/a Miami Children's Hospital at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages Up to 22 years
Conditions the study is for: Recurrent Childhood Medulloblastoma, Recurrent Childhood Ependymoma, Childhood Atypical Teratoid/Rhabdoid Tumor
What is being tested?: Intra thecal methotrexate, topotecan and cyclophosphamide
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: 1 siteUnited States
Study dates: Feb 2016to 9 Dec 2019
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 22 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.

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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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Nicklaus Children's Hospital
Miami, Florida, 33155

Other trials in United States

About this study

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

Read the 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.

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
Being tested: Intra thecal methotrexate, topotecan, cyclophosphamide
Keywords: medulloblastoma, ependymoma, AT/RT, embryonal
Medical subject headings: Medulloblastoma, Familial ependymoma, Rhabdoid Tumor, Neuroectodermal Tumors, Primitive, Meningeal Carcinomatosis, Ependymoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Intra thecal methotrexateDrug
Also called Intra thecal methotrexate, topotecan and cyclophosphamide
IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide
topotecanDrug
Also called Intra thecal methotrexate, topotecan and cyclophosphamide
To be administered in conjunction with methotrexate
cyclophosphamideDrug
Also called Intra thecal methotrexate, topotecan and cyclophosphamide
To be administered in conjunction with methotrexate and topotecan

Study groups in NCT02684071
Study group	Role	What they receive
Intra thecal methotrexate	Experimental	IT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide Receives: Drug: Intra thecal methotrexate; Drug: topotecan; Drug: cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

Tumor response
MRI response
Measured: 6 months

Secondary outcomes (1)

Toxicity of chemotherapy regimen (topotecan and cyclophosphamide)
Laboratory results, MRI, physical examination
Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 20169 Dec 2019

First posted17 Feb 2016 (estimated)
Study startFeb 2016
Primary completion9 Dec 2019
Study completion9 Dec 2019

Why it stopped: Lack of additional funding; patients (3) no longer receiving intervention.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Recurrent Childhood MedulloblastomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02684071
Sponsor's protocol ID: NCH-CNS-1601
Status last verified: Jan 2020
First submitted: 11 Feb 2016
Last updated: 10 Jan 2020
Results posted: No
Data monitoring committee: Yes
Individual data sharing: No

Publications

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.
PubMed 16533779
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.
PubMed 9696374
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.
PubMed 18057943
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.
PubMed 20440538
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.
PubMed 19688296
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.
PubMed 18447671

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 10 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Study of Intraventricular Methotrexate With Systemic Topotecan and Cyclophosphamide in Children With Recurrent or Progressive Malignant Brain Tumors
ClinicalTrials.gov ID: NCT02684071
Acronym / sponsor ID: NCH-CNS-1601
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
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Lack of additional funding; patients (3) no longer receiving intervention.
Enrolment: 3 participants (actual)
Lead sponsor: Nicklaus Children's Hospital f/k/a Miami Children's HospitalUniversity, hospital or other
Study start: Feb 2016 (actual)
Primary completion: 9 Dec 2019 (actual)
Study completion: 9 Dec 2019 (actual)
First posted: 17 Feb 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Intra thecal methotrexate	Experimental	Drug: Intra thecal methotrexate, Drug: topotecan, Drug: cyclophosphamideIT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide

Who may qualify

Ages: Up to 22 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (9 listed)

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.

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Intra thecal methotrexateAlso: Intra thecal methotrexate, topotecan and cyclophosphamideIT methotrexate via Ommaya reservoir with concomitant systemic topotecan and cyclophosphamide	Drug	Intra thecal methotrexate
topotecanAlso: Intra thecal methotrexate, topotecan and cyclophosphamideTo be administered in conjunction with methotrexate	Drug	Intra thecal methotrexate
cyclophosphamideAlso: Intra thecal methotrexate, topotecan and cyclophosphamideTo be administered in conjunction with methotrexate and topotecan	Drug	Intra thecal methotrexate

Primary outcome

Tumor response
Time frame: 6 months
MRI response

1 secondary outcome

Toxicity of chemotherapy regimen (topotecan and cyclophosphamide)
Time frame: 6 months

Results and safety

The study was stopped early (reason given: Lack of additional funding; patients (3) no longer receiving intervention.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2020.
Background: PubMed 16533779Gururangan 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.
Background: PubMed 9696374Slavc 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.
Background: PubMed 18057943Yoshimura 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.
Background: PubMed 20440538Sandberg 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.
Background: PubMed 19688296Sandberg 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 publication: PubMed 18447671Sandberg 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.
Nicklaus Children's Hospital Cancer CenterLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Recurrent Childhood Medulloblastoma

Active, not recruitingPhase 2
Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Recurrent Childhood Ependymoma
RecruitingPhase 1
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RecruitingPhase 1
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ziad Khatib, MD principal investigator

Nicklaus Children's Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Lack of additional funding; patients (3) no longer receiving intervention.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tumor response (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02684071, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2020.