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Trial record 1 of 1 for:    NCT00653068
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Combination Chemotherapy, Radiation Therapy, and an Autologous Peripheral Blood Stem Cell Transplant in Treating Young Patients With Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00653068
Recruitment Status : Active, not recruiting
First Posted : April 4, 2008
Results First Posted : February 13, 2017
Last Update Posted : February 5, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:
This phase III trial studies the side effects of combination chemotherapy, 3-dimensional conformal radiation therapy, and an autologous peripheral blood stem cell transplant, and to see how well they work in treating young patients with atypical teratoid/rhabdoid tumor of the central nervous system. Giving high-dose chemotherapy before an autologous peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy or radiation therapy.

Condition or disease Intervention/treatment Phase
Childhood Atypical Teratoid/Rhabdoid Tumor Radiation: 3-Dimensional Conformal Radiation Therapy Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Carboplatin Drug: Cisplatin Drug: Cyclophosphamide Drug: Etoposide Biological: Filgrastim Other: Laboratory Biomarker Analysis Drug: Leucovorin Calcium Drug: Methotrexate Drug: Thiotepa Drug: Vincristine Sulfate Phase 3

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Atypical Teratoid/Rhabdoid Tumors (AT/RT) of the Central Nervous System With Surgery, Intensive Chemotherapy, and 3-D Conformal Radiation
Actual Study Start Date : December 8, 2008
Actual Primary Completion Date : September 27, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm I (chemotherapy, autologous PBSC, 3D-CRT)

Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.

Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.

Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
Other Names:
  • 3-dimensional radiation therapy
  • 3D CONFORMAL RADIATION THERAPY
  • 3D CRT
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy

Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC rescue
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • autologous stem cell transplantation

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213

Biological: Filgrastim
Given IV or SC
Other Names:
  • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Leucovorin Calcium
Given IV or PO
Other Names:
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • citrovorum factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • folinic acid
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Wellcovorin

Drug: Methotrexate
Given IV
Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039

Drug: Thiotepa
Given IV
Other Names:
  • 1,1',1''-Phosphinothioylidynetrisaziridine
  • Girostan
  • N,N', N''-Triethylenethiophosphoramide
  • Oncotiotepa
  • STEPA
  • Tepadina
  • TESPA
  • Tespamin
  • Tespamine
  • Thio-Tepa
  • Thiofosfamide
  • Thiofozil
  • Thiophosphamide
  • Thiophosphoramide
  • Thiotef
  • Tifosyl
  • TIO TEF
  • Tio-tef
  • Triethylene thiophosphoramide
  • Triethylenethiophosphoramide
  • Tris(1-aziridinyl)phosphine sulfide
  • TSPA
  • WR 45312

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate

Experimental: Arm II (chemotherapy, 3D-CRT, autologous PBSC)

Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.

Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
Other Names:
  • 3-dimensional radiation therapy
  • 3D CONFORMAL RADIATION THERAPY
  • 3D CRT
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy

Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC rescue
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • autologous stem cell transplantation

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213

Biological: Filgrastim
Given IV or SC
Other Names:
  • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Leucovorin Calcium
Given IV or PO
Other Names:
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • citrovorum factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • folinic acid
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Wellcovorin

Drug: Methotrexate
Given IV
Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039

Drug: Thiotepa
Given IV
Other Names:
  • 1,1',1''-Phosphinothioylidynetrisaziridine
  • Girostan
  • N,N', N''-Triethylenethiophosphoramide
  • Oncotiotepa
  • STEPA
  • Tepadina
  • TESPA
  • Tespamin
  • Tespamine
  • Thio-Tepa
  • Thiofosfamide
  • Thiofozil
  • Thiophosphamide
  • Thiophosphoramide
  • Thiotef
  • Tifosyl
  • TIO TEF
  • Tio-tef
  • Triethylene thiophosphoramide
  • Triethylenethiophosphoramide
  • Tris(1-aziridinyl)phosphine sulfide
  • TSPA
  • WR 45312

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate




Primary Outcome Measures :
  1. Event-free Survival [ Time Frame: Up to 4 years after study enrollment ]
    Estimated 4-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.

  2. Overall Survival (OS) [ Time Frame: Up to 4 years after study enrollment ]
    Estimated 4-year survival, where survival is calculated as the time from study enrollment to death from any cause or last follow-up alive whichever occurs first. Kaplan-Meier method is used for estimation. Patients alive at last contact are censored.

  3. Toxic Death [ Time Frame: During and after completion of study treatment up to 1 year after enrollment. ]
    The number of patients who experience death that is considered to be primarily attributable to complications of treatment.


Secondary Outcome Measures :
  1. Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy [ Time Frame: During protocol therapy up to 1 year after enrollment. ]
    Number of Participants with Nonhematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of CNS atypical teratoid/rhabdoid tumor (AT/RT) or tumors that have a mutation of the INI1 gene (even if the tumor does not have the usual histologic characteristics of AT/RT)

    • Patients with extra neural metastasis (M4) or renal rhabdoid tumors are not eligible
    • Patients with MRI evidence of spinal disease are eligible
  • Must have undergone definitive surgery in the past 31 days
  • Cranial MRI (with and without gadolinium) must be done pre-operatively

    • Post-operatively, cranial MRI (with and without gadolinium) must be done, preferably within 48 hours of surgery or 10-28 days after surgery
  • Entire spinal MRI must be obtained either pre-operatively (with gadolinium) or post-operatively (10-28 days after surgery), prior to study enrollment (with and without gadolinium)
  • Life expectancy > 8 weeks
  • ANC > 1,000/uL
  • Platelet count > 100,000/uL (transfusion independent)
  • Hemoglobin > 8 g/dL (RBC transfusions allowed)
  • Creatinine clearance (minimum of 12-24 hour urine collection) or radioisotope GFR >= 60 mL/min
  • Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
  • AST and ALT < 2 times ULN for age
  • Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 47% by radionuclide angiogram
  • No evidence of dyspnea at rest
  • Pulse oximetry > 94% on room air
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior radiotherapy or chemotherapy except for the following:

    • Patients enrolled on protocol ACNS0334 whose tumors demonstrate the INI1 gene mutation are eligible to transfer to this study even if they have received one course of induction therapy (these patients must be re-consented to treatment and restaged)
    • Prior corticosteroids allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00653068


  Show 94 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Alyssa Reddy Children's Oncology Group

Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00653068     History of Changes
Other Study ID Numbers: ACNS0333
NCI-2009-00337 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ACNS0333
09-0058
CDR0000592812
COG-ACNS0333
ACNS0333 ( Other Identifier: Childrens Oncology Group )
ACNS0333 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: April 4, 2008    Key Record Dates
Results First Posted: February 13, 2017
Last Update Posted: February 5, 2019
Last Verified: September 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Rhabdoid Tumor
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Neoplasms
Calcium, Dietary
Leucovorin
Folic Acid
Cisplatin
Cyclophosphamide
Carboplatin
Methotrexate
Etoposide
Etoposide phosphate
Vincristine
Thiotepa
Lenograstim
Calcium
Levoleucovorin
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Calcium-Regulating Hormones and Agents
Bone Density Conservation Agents
Abortifacient Agents, Nonsteroidal