Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctors to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating infants with malignant brain or spinal cord tumors.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Mar 1998

Longer than P75 for phase_1

Geographic Reach

3 countries

71 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

13.6 years study duration

Study Start

First participant enrolled

March 1, 1998

Completed

1.7 years until next milestone

First Submitted

Initial submission to the registry

November 1, 1999

Completed

4 years until next milestone

First Posted

Study publicly available on registry

November 6, 2003

Completed

4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2007

Completed

3.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2011

Completed

Last Updated

March 28, 2014

Status Verified

March 1, 2014

Enrollment Period

9.8 years

First QC Date

November 1, 1999

Last Update Submit

March 27, 2014

Conditions

Brain Tumors Central Nervous System Tumors Neuroblastoma Sarcoma

Keywords

childhood infratentorial ependymomachildhood supratentorial ependymomadisseminated neuroblastomastage 4S neuroblastomaembryonal childhood rhabdomyosarcomachildhood high-grade cerebral astrocytomachildhood choroid plexus tumorpreviously untreated childhood rhabdomyosarcomauntreated childhood brain stem gliomauntreated childhood supratentorial primitive neuroectodermal tumoruntreated childhood cerebellar astrocytomauntreated childhood medulloblastomanewly diagnosed childhood ependymomalocalized resectable neuroblastomalocalized unresectable neuroblastomaregional neuroblastomachildhood spinal cord neoplasmchildhood atypical teratoid/rhabdoid tumorchildhood low-grade cerebral astrocytomachildhood central nervous system choriocarcinomachildhood central nervous system embryonal tumorchildhood central nervous system germinomachildhood central nervous system mixed germ cell tumorchildhood central nervous system teratomachildhood central nervous system yolk sac tumor

Outcome Measures

Primary Outcomes (3)

Feasibility
Demonstrate the feasibility of administering this regimen, to select an acceptable Thiotepa dose for Consolidation therapy, and to document significant toxicities and estimate their overall rates
Up to 4 weeks after completion of study treatment
Maximal tolerated dose of thiotepa for consolidation therapy
The dose level will be assigned within 3 working days prior to beginning Consolidation.
9 weeks
Overall rates of significant toxicities including grade IV ototoxicity, electrolytic wasting (grade IV), and hemorrhagic cystitis (grade IV)
Estimates will be obtained using life-table methods with an event defined as the first occurrence of toxicity. Graded using the CCG Toxicity and Complications Criteria.
Up to 6 years

Secondary Outcomes (1)

Event Free Survival
From the time of study entry to the first occurrence of death by any cause, progression or recurrence of disease or occurrence of a second malignant neoplasm, assessed up

Study Arms (1)

Treatment (combination chemotherapy, PBSC transplant)

EXPERIMENTAL

Pts undergo conventional surgery for diagnosis \& max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) \& undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse.

Biological: filgrastimDrug: carboplatinDrug: cisplatinDrug: cyclophosphamideDrug: etoposideDrug: thiotepaDrug: vincristine sulfateProcedure: conventional surgeryProcedure: peripheral blood stem cell transplantation