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Trial record 30 of 115 for:    cancer | butyrate

Chemotherapy Combined With Radiation Therapy for Newly Diagnosed CNS AT/RT

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ClinicalTrials.gov Identifier: NCT00084838
Recruitment Status : Completed
First Posted : June 11, 2004
Results First Posted : December 24, 2015
Last Update Posted : December 24, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mark W. Kieran, MD, PhD, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Central Nervous System Tumor, Pediatric
Interventions Biological: filgrastim
Drug: cisplatin
Drug: cyclophosphamide
Drug: cytarabine
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: leucovorin calcium
Drug: methotrexate
Drug: temozolomide
Drug: therapeutic hydrocortisone
Drug: vincristine sulfate
Radiation: radiation therapy
Drug: Dactinomycin
Enrollment 25
Recruitment Details Enrollment Sep 2004 to Sep 2006 at 9 institutions.
Pre-assignment Details  
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Modified IRS
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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.

Period Title: Overall Study
Started 25
Eligible and Treated 20 [1]
Completed 12
Not Completed 13
Reason Not Completed
Death             1
Adverse Event             2
Withdrawal by Subject             1
Progressive Disease             4
Pt Non-Compliance             1
Ineligible             4
[1]
4 ineligible pts upon central path review (n=3) and per DFCI IRB (n=1); 1 pt withdrew before rcv trt
Arm/Group Title Multi-agent Intrathecal & Systemic CT w/ RT (Modified IRS III)
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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.

Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 20 participants
2.2
(0.2 to 19)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
11
  55.0%
Male
9
  45.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants
20
Chang Stage   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 20 participants
M0 14
M2 1
M3 5
[1]
Measure Description: Chang staging: M0 is non-metastatic disease. M1 is CSF +ve disease which means that the tumor cells are found floating in the spinal fluid, M2 is localized metastatic disease and M3 is disseminated bulk disease.
1.Primary Outcome
Title 2-yr Overall Survival
Hide Description 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all eligible and treated patients.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Modified IRS
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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.

Overall Number of Participants Analyzed 20
Measure Type: Number
Unit of Measure: probability
0.70
2.Secondary Outcome
Title Pre-Radiation Therapy Chemotherapeutic Response
Hide Description

Response pre-RT/post-CT was defined as follows with overall response defined as achieving PR or CR.

Complete Response (CR): Complete resolution of all initially demonstrable tumor on MRI or CT evaluation w/o appearance of any new areas of disease; negative CSF cytology. Partial Response (PR): >/= 50% decrease in the sum of the products of the maximum perpendicular diameters of the tumor (sum LD) relative to baseline w/o appearance of any new areas of disease; CSF cytology unchanged from that at diagnosis or clearing after being initially positive Stable Disease (SD): <50% decrease in the sum LD w/o appearance of any new areas of disease; CSF cytology unchanged from that at diagnosis or clearing after being initially positive Progressive Disease (PD): >/= 25% increase in the sum LD relative to baseline, or the appearance of any new areas of disease or appearance of positive cytology after two consecutive negative samples.

Time Frame Assessed at study entry and pre-RT/post-CT at week 7.
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Hide Analysis Population Description
The pre-RT CT response evaluable population is defined as patients who completed chemotherapy per protocol.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Modified IRS
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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.

Overall Number of Participants Analyzed 12
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of evaluable patients
0.58
(0.32 to 0.82)
3.Other Pre-specified Outcome
Title Grade 3/4 Events
Hide Description All Grade 3-4 events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
1021
4.Other Pre-specified Outcome
Title Grade 3-4 Auditory/Hearing Events
Hide Description All Grade 3-4 Auditory/Hearing events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
8
5.Other Pre-specified Outcome
Title Grade 3-4 Blood/Bone Marrow Events
Hide Description

All Grade 3-4 Blood/Bone Marrow events based on CTCAEv2 as reported on case report forms.

Arm Name

Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
564
6.Other Pre-specified Outcome
Title Grade 3-4 Gastrointestinal Events
Hide Description All Grade 3-4 Gastrointestinal events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
139
7.Other Pre-specified Outcome
Title Grade 3-4 Metabolic/Laboratory Events
Hide Description All Grade 3-4 Metabolic/Laboratory events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
128
8.Other Pre-specified Outcome
Title Grade 3-4 Infection/Febrile Neutropenia Events
Hide Description All Grade 3-4 Infection/Febrile Neutropenia events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
49
9.Other Pre-specified Outcome
Title Grade 3-4 Neurology Events
Hide Description All Grade 3-4 Neurology events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
45
10.Other Pre-specified Outcome
Title Grade 3-4 Pain Events
Hide Description All Grade 3-4 Pain events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
31
11.Other Pre-specified Outcome
Title Grade 3-4 Constitutional Events
Hide Description All Grade 3-4 Constitutional events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
22
12.Other Pre-specified Outcome
Title Grade 3-4 Muscloskeletal Events
Hide Description All Grade 3-4 Muscloskeletal events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
8
13.Other Pre-specified Outcome
Title Grade 3-4 Hepatic Events
Hide Description All Grade 3-4 Hepatic events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
8
14.Other Pre-specified Outcome
Title Grade 3-4 Cardiovascular Events
Hide Description All Grade 3-4 Cardiovascular events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
6
15.Other Pre-specified Outcome
Title Grade 3-4 Pulmonary Events
Hide Description All Grade 3-4 Pulmonary events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
4
16.Other Pre-specified Outcome
Title Grade 3-4 Renal/Genitourinary Events
Hide Description All Grade 3-4 Renal/Genitourinary events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
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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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
4
17.Other Pre-specified Outcome
Title Grade 3-4 Dermatology Events
Hide Description All Grade 3-4 Dermatology events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
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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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
3
18.Other Pre-specified Outcome
Title Grade 3-4 Hemorrhage Events
Hide Description All Grade 3-4 Hemorrhage events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
1
19.Other Pre-specified Outcome
Title Grade 3-4 Allergy/Immunology
Hide Description All Grade 3-4 Allergy/Immunology events based on CTCAEv2 as reported on case report forms.
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population excludes 1 patient who withdrew before treatment.
Arm/Group Title Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III)
Hide Arm/Group Description:

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.

filgrastim

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: adverse events
1
Time Frame Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
Adverse Event Reporting Description SAEs were grade 3+ unexpected, treatment-related events deemed notable by the study chair. Accessible adverse event data represents a count of events by toxicity type rather than worst-grade by toxicity type and therefore cannot be reported in the established framework (Affected/At Risk). See secondary outcomes for events by system organ class.
 
Arm/Group Title Multi-agent Intrathecal & Systemic CT w/ RT (Modified IRS III)
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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.

All-Cause Mortality
Multi-agent Intrathecal & Systemic CT w/ RT (Modified IRS III)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Multi-agent Intrathecal & Systemic CT w/ RT (Modified IRS III)
Affected / at Risk (%) # Events
Total   4/20 (20.00%)    
Infections and infestations   
Sepsis  1 [1]  1/20 (5.00%)  1
Nervous system disorders   
Radiation recall  1  2/20 (10.00%)  2
Transverse Myeolitis  1  1/20 (5.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAEv2
[1]
Patient died of pneumococcal sepsis
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Multi-agent Intrathecal & Systemic CT w/ RT (Modified IRS III)
Affected / at Risk (%) # Events
Total   0/0    
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Mark Kieran
Organization: Dana-Farber Cancer Institute
Phone: (617) 632-4907
EMail: mark_kieran@dfci.harvard.edu
Layout table for additonal information
Responsible Party: Mark W. Kieran, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00084838     History of Changes
Other Study ID Numbers: 02-294 DFCI
P30CA006516 ( U.S. NIH Grant/Contract )
First Submitted: June 10, 2004
First Posted: June 11, 2004
Results First Submitted: December 14, 2012
Results First Posted: December 24, 2015
Last Update Posted: December 24, 2015