Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving more than one chemotherapy drug with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving intrathecal and systemic combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system (CNS) atypical teratoid/rhabdoid tumors.

Trial Health

On Track

Trial Health Score

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

Enrollment

participants targeted

Target at below P25 for phase_2

Timeline

Completed

Started Feb 2003

Longer than P75 for phase_2

Geographic Reach

1 country

12 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

10.1 years study duration

Study Start

First participant enrolled

February 1, 2003

Completed

1.4 years until next milestone

First Submitted

Initial submission to the registry

June 10, 2004

Completed

1 day until next milestone

First Posted

Study publicly available on registry

June 11, 2004

Completed

3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2008

Completed

5.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2013

Completed

2.8 years until next milestone

Results Posted

Study results publicly available

December 24, 2015

Completed

Last Updated

December 24, 2015

Status Verified

December 1, 2015

Enrollment Period

5 years

First QC Date

June 10, 2004

Results QC Date

December 14, 2012

Last Update Submit

December 18, 2015

Conditions

Central Nervous System Tumor, Pediatric

Keywords

childhood atypical teratoid/rhabdoid tumor

Outcome Measures

Primary Outcomes (1)

2-yr Overall Survival
Overall survival is defined as the time from date of diagnosis to death or date of last follow-up. 2-year overall survival is the probability of patients remaining alive at 2-years from study entry estimated using Kaplan-Meier (KM) methods which censors patients at date of last follow-up. Precision of this conditional probability estimate was measured in terms of standard error. Median OS, the original primary endpoint, was not estimable based on the Kaplan-Meier method because of insufficient follow-up.
Patients are followed for survival up to 5 yrs post-therapy completion or death; As of this analysis, median follow-up among survivors was 31 months with the longest follow-up being 40 months.

Secondary Outcomes (1)

Pre-Radiation Therapy Chemotherapeutic Response
Assessed at study entry and pre-RT/post-CT at week 7.

Other Outcomes (17)

Grade 3/4 Events
Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Grade 3-4 Auditory/Hearing Events
Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Grade 3-4 Blood/Bone Marrow Events
Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
+14 more other outcomes

Study Arms (1)

Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)

EXPERIMENTAL

Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.

Biological: filgrastimDrug: cisplatinDrug: cyclophosphamideDrug: cytarabineDrug: dexrazoxane hydrochlorideDrug: doxorubicin hydrochlorideDrug: etoposideDrug: leucovorin calciumDrug: methotrexateDrug: temozolomideDrug: therapeutic hydrocortisoneDrug: vincristine sulfateRadiation: radiation therapyDrug: Dactinomycin