Childhood Atypical Teratoid/Rhabdoid TumorPhase 3NCT00653068
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
A Phase 3 study testing 3-Dimensional Conformal Radiation Therapy, Autologous Hematopoietic Stem Cell Transplantation and Carboplatin in people with Childhood Atypical Teratoid/Rhabdoid Tumor, run by Children's Oncology Group at 94 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Childhood Atypical Teratoid/Rhabdoid Tumor
- What is being tested?
- 3-Dimensional Conformal Radiation Therapy, Autologous Hematopoietic Stem Cell Transplantation and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 94 sitesin 3 countries
- Study dates
- 10 Feb 2009to 31 Mar 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 23Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
94 sites in 3 countries.
94 sites in 3 countries
United States87 sites
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102
Mission Hospital
Asheville, North Carolina, 28801
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Children's Hospital of Alabama
Birmingham, Alabama, 35233
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
West Virginia University Charleston Division
Charleston, West Virginia, 25304
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
Nationwide Children's Hospital
Columbus, Ohio, 43205
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Dayton Children's Hospital
Dayton, Ohio, 45404
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Kaiser Permanente Downey Medical Center
Downey, California, 90242
Lee Memorial Health System
Fort Myers, Florida, 33901
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Cook Children's Medical Center
Fort Worth, Texas, 76104
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Greenville Cancer Treatment Center
Greenville, South Carolina, 29605
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Norton Children's Hospital
Louisville, Kentucky, 40202
Valley Children's Hospital
Madera, California, 93636
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Loyola University Medical Center
Maywood, Illinois, 60153
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
Morristown Medical Center
Morristown, New Jersey, 07960
Tulane University School of Medicine
New Orleans, Louisiana, 70112
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
Children's Hospital of Orange County
Orange, California, 92868
AdventHealth Orlando
Orlando, Florida, 32803
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806
Orlando Health Cancer Institute
Orlando, Florida, 32806
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Rhode Island Hospital
Providence, Rhode Island, 02903
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
Primary Children's Hospital
Salt Lake City, Utah, 84113
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
UCSF Medical Center-Parnassus
San Francisco, California, 94143
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63110
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Overlook Hospital
Summit, New Jersey, 07902
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Mercy Children's Hospital
Toledo, Ohio, 43608
New York Medical College
Valhalla, New York, 10595
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Saint Mary's Hospital
West Palm Beach, Florida, 33407
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Canada5 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Australia2 sites
Royal Children's Hospital
Parkville, Victoria, 3052
Princess Margaret Hospital for Children
Perth, Western Australia, 6008
About this study
Official title: Treatment of Atypical Teratoid/Rhabdoid Tumors (AT/RT) of the Central Nervous System With Surgery, Intensive Chemotherapy, and 3-D Conformal Radiation
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the 6-, 12-, and 24-month event-free survival and overall survival of children (birth to 21 years of age) with atypical teratoid/rhabdoid CNS tumors (AT/RT), diagnosed based on histology, immunophenotyping, and modern molecular and immunohistochemical analysis of INI1, treated with surgery, intensive chemotherapy combined with stem cell rescue, and radiation therapy.
II. To compare the outcome of very young patients (under 3 years old) on this study whose histologic diagnosis is AT/RT with infants identified as having AT/RT on POG-9233 and CCG-9921.
SECONDARY OBJECTIVES:
- To determine the feasibility and toxicity of the proposed chemotherapy regimen in combination with radiation therapy.
II. To contribute tumor samples from which biologic and gene expression data can be developed to yield prognostic indicators and provide direction for future treatment strategies.
III. To develop a clinical and biologic database on which future studies can be based.
OUTLINE:
INDUCTION THERAPY AND STEM CELL HARVEST: Patients receive vincristine IV on days 1, 8, and 15 and high-dose methotrexate IV over 4 hours on day 1. Beginning 24 hours after the start of methotrexate, patients receive leucovorin calcium orally (PO) or IV every 6 hours until the serum methotrexate level is < 0.1 micromoles. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6*. Patients also receive filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 7 and continuing until ANC recovers. When ANC is > 1,000/uL post nadir, patients receive G-CSF twice daily for stem cell mobilization. Approximately 2-4 days, later peripheral blood stem cells are harvested once daily, as needed, after each course of induction therapy until a total of 6 x 10^6 CD34+ cells/kg have been collected. Treatment repeats every 21 days for 2 courses.
After completion of induction therapy, patients are re-evaluated. Patients with progressive disease are removed from study. Patients with radiographic evidence of residual tumor are encouraged to undergo second-look surgery prior to proceeding to radiotherapy or consolidation therapy; patients with complete response, partial response, or stable disease are assigned to 1 of 2 arm.
ARM I ((patients less than 6 months, infratentorial site with M0 involvement or patients less than 12 months, supratentorial site with M0 involvement or patients with disseminated disease of any primary site or age):
CONSOLIDATION THERAPY AND STEM CELL RESCUE: Within 2-6 weeks after completion of induction therapy, patients begin consolidation therapy. Patients receive high-dose carboplatin IV over 4 hours and high-dose thiotepa IV over 2 hours on days 1 and 2 and undergo autologous peripheral blood stem cell (PBSC) rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily beginning 24 hours after stem cell infusion and continuing 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.
RADIATION THERAPY: Patients undergo 3-dimensional conformal radiotherapy (3D-CRT) to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
ARM II (patients greater than or equal to 6 months, infratentorial site with M0 involvement or patients greater than or equal to 12 months, supratentorial site with M0 involvement): Patients undergo 3D-CRT as in Arm I. Within 2-6 weeks after completion of radiation therapy, patients receive consolidation therapy and stem cell rescue as in Arm I
NOTE: *The administration of etoposide, cyclophosphamide, and cisplatin are dependant on the prior clearance of methotrexate to a level of < 0.1 micromoles.
After completion of study treatment, patients are followed periodically for up to 10 years.
- Being tested
- 3-Dimensional Conformal Radiation Therapy, Autologous Hematopoietic Stem Cell Transplantation, Carboplatin, Cisplatin, Cyclophosphamide
- Medical subject headings
- Rhabdoid Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3-Dimensional Conformal Radiation TherapyRadiation
Also called 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT
Undergo 3D-CRT
Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplant
Undergo autologous PBSC rescue
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
CisplatinDrug
Also called Abiplatin, Blastolem, Briplatin, CDDP
Given IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518
Given IV
EtoposideDrug
Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar
Given IV
FilgrastimBiological
Also called Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi
Given IV or SC
Laboratory Biomarker AnalysisOther
Correlative studies
Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate
Given IV or PO
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IV
ThiotepaDrug
Also called 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa
Given IV
Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (chemotherapy, autologous PBSC, 3D-CRT) | Experimental | 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. Receives: 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 |
| Arm II (chemotherapy, 3D-CRT, autologous PBSC) | Experimental | 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free Survival
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.
Measured: Up to 4 years after study enrollment
Overall Survival (OS)
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.
Measured: Up to 4 years after study enrollment
Toxic Death
The number of patients who experience death that is considered to be primarily attributable to complications of treatment.
Measured: During and after completion of study treatment up to 1 year after enrollment.
Secondary outcomes (1)
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy
Number of Participants with Nonhematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy.
Measured: During protocol therapy up to 1 year after enrollment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2008 (estimated)
- Study start10 Feb 2009
- Primary completion27 Sep 2016
- Study completion31 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Childhood Atypical Teratoid/Rhabdoid TumorStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Alyssa T Reddy, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00653068
- Sponsor's protocol ID
- ACNS0333
- Other IDs
- NCI-2009-00337, CDR0000592812, 09-0058, COG-ACNS0333, ACNS0333, ACNS0333, U10CA098543, U10CA180886
- Status last verified
- Apr 2024
- First submitted
- 3 Apr 2008
- Last updated
- 23 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Mazzarella J, Heathcock JC. A Randomized Feasibility Study of Rehabilitation Targeting Upper Extremity Function and Participation Using Hippotherapy and the Equine Environment for Children with Cerebral Palsy and Autism Spectrum Disorder. J Integr Complement Med. 2025 Feb;31(2):196-208. doi: 10.1089/jicm.2024.0292. Epub 2024 Nov 8.
PubMed 39515374Reddy AT, Krailo MD, Buxton AB, Strother DR, Huang A, Zhou T, Judkins AR, Burger PC, Pollack IF, Williams-Hughes C, Fouladi M, Ho B, Mazewski CM, Lewis VA, Vezina LG, Booth TN, Mahajan A. Reply to S.A. Upadhyaya. J Clin Oncol. 2020 Oct 1;38(28):3353-3354. doi: 10.1200/JCO.20.01573. Epub 2020 Jul 30. No abstract available.
PubMed 32730180
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Atypical Teratoid/Rhabdoid Tumors (AT/RT) of the Central Nervous System With Surgery, Intensive Chemotherapy, and 3-D Conformal Radiation
- ClinicalTrials.gov ID
- NCT00653068
- Acronym / sponsor ID
- ACNS0333
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 10 Feb 2009 (actual)
- Primary completion
- 27 Sep 2016 (actual)
- Study completion
- 31 Mar 2024 (actual)
- First posted
- 4 Apr 2008 (estimated)
- Results
- Posted 13 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To determine the 6-, 12-, and 24-month event-free survival and overall survival of children (birth to 21 years of age) with atypical teratoid/rhabdoid CNS tumors (AT/RT), diagnosed based on histology, immunophenotyping, and modern molecular and immunohistochemical analysis of INI1, treated with surgery, intensive chemotherapy combined with stem cell rescue, and radiation therapy.
II. To compare the outcome of very young patients (under 3 years old) on this study whose histologic diagnosis is AT/RT with infants identified as having AT/RT on POG-9233 and CCG-9921.
SECONDARY OBJECTIVES:
- To determine the feasibility and toxicity of the proposed chemotherapy regimen in combination with radiation therapy.
II. To contribute tumor samples from which biologic and gene expression data can be developed to yield prognostic indicators and provide direction for future treatment strategies.
III. To develop a clinical and biologic database on which future studies can be based.
OUTLINE:
INDUCTION THERAPY AND STEM CELL HARVEST: Patients receive vincristine IV on days 1, 8, and 15 and high-dose methotrexate IV over 4 hours on day 1. Beginning 24 hours after the start of methotrexate, patients receive leucovorin calcium orally (PO) or IV every 6 hours until the serum methotrexate level is < 0.1 micromoles. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6*. Patients also receive filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 7 and continuing until ANC recovers. When ANC is > 1,000/uL post nadir, patients receive G-CSF twice daily for stem cell mobilization. Approximately 2-4 days, later peripheral blood stem cells are harvested once daily, as needed, after each course of induction therapy until a total of 6 x 10^6 CD34+ cells/kg have been collected. Treatment repeats every 21 days for 2 courses.
After completion of induction therapy, patients are re-evaluated. Patients with progressive disease are removed from study. Patients with radiographic evidence of residual tumor are encouraged to undergo second-look surgery prior to proceeding to radiotherapy or consolidation therapy; patients with complete response, partial response, or stable disease are assigned to 1 of 2 arm.
ARM I ((patients less than 6 months, infratentorial site with M0 involvement or patients less than 12 months, supratentorial site with M0 involvement or patients with disseminated disease of any primary site or age):
CONSOLIDATION THERAPY AND STEM CELL RESCUE: Within 2-6 weeks after completion of induction therapy, patients begin consolidation therapy. Patients receive high-dose carboplatin IV over 4 hours and high-dose thiotepa IV over 2 hours on days 1 and 2 and undergo autologous peripheral blood stem cell (PBSC) rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily beginning 24 hours after stem cell infusion and continuing 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.
RADIATION THERAPY: Patients undergo 3-dimensional conformal radiotherapy (3D-CRT) to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
ARM II (patients greater than or equal to 6 months, infratentorial site with M0 involvement or patients greater than or equal to 12 months, supratentorial site with M0 involvement): Patients undergo 3D-CRT as in Arm I. Within 2-6 weeks after completion of radiation therapy, patients receive consolidation therapy and stem cell rescue as in Arm I
NOTE: *The administration of etoposide, cyclophosphamide, and cisplatin are dependant on the prior clearance of methotrexate to a level of < 0.1 micromoles.
After completion of study treatment, patients are followed periodically for up to 10 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (chemotherapy, autologous PBSC, 3D-CRT) | Experimental | 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 SulfatePatients 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. |
| Arm II (chemotherapy, 3D-CRT, autologous PBSC) | Experimental | 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 SulfatePatients 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. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (23 listed)
- 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)
- Must have undergone definitive surgery in the past 31 days
- Cranial MRI (with and without gadolinium) must be done pre-operatively
- 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
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| 3-Dimensional Conformal Radiation TherapyAlso: 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRTUndergo 3D-CRT | Radiation | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
| Autologous Hematopoietic Stem Cell TransplantationAlso: AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell TransplantUndergo autologous PBSC rescue | Procedure or surgery | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
| CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven IV | Drug | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
| CisplatinAlso: Abiplatin, Blastolem, Briplatin, CDDPGiven IV | Drug | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518Given IV | Drug | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
| EtoposideAlso: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, ToposarGiven IV | Drug | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
| FilgrastimAlso: Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafiGiven IV or SC | Biological | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
| Leucovorin CalciumAlso: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium FolinateGiven IV or PO | Drug | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
| MethotrexateAlso: Abitrexate, Alpha-Methopterin, Amethopterin, BrimexateGiven IV | Drug | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
| ThiotepaAlso: 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, OncotiotepaGiven IV | Drug | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
| Vincristine SulfateAlso: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, OncovinGiven IV | Drug | Arm I (chemotherapy, autologous PBSC, 3D-CRT), Arm II (chemotherapy, 3D-CRT, autologous PBSC) |
Primary outcome
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.
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.
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.
1 secondary outcome
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy
Time frame: During protocol therapy up to 1 year after enrollment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39515374Mazzarella J, Heathcock JC. A Randomized Feasibility Study of Rehabilitation Targeting Upper Extremity Function and Participation Using Hippotherapy and the Equine Environment for Children with Cerebral Palsy and Autism Spectrum Disorder. J Integr Complement Med. 2025 Feb;31(2):196-208. doi: 10.1089/jicm.2024.0292. Epub 2024 Nov 8.
- Derived from this study: PubMed 32730180Reddy AT, Krailo MD, Buxton AB, Strother DR, Huang A, Zhou T, Judkins AR, Burger PC, Pollack IF, Williams-Hughes C, Fouladi M, Ho B, Mazewski CM, Lewis VA, Vezina LG, Booth TN, Mahajan A. Reply to S.A. Upadhyaya. J Clin Oncol. 2020 Oct 1;38(28):3353-3354. doi: 10.1200/JCO.20.01573. Epub 2020 Jul 30. No abstract available.
- Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data ArchiveLink provided by the sponsor.
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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.
Alyssa T Reddy principal investigator
Children's Oncology Group
94 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 3-Dimensional Conformal Radiation Therapy, Autologous Hematopoietic Stem Cell Transplantation and Carboplatin in people with Childhood Atypical Teratoid/Rhabdoid Tumor, run by Children's Oncology Group at 94 sites in 3 countries.
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 23 inclusion and 0 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: finished, as of the sponsor's last update on 23 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 94 sites in United States, Canada, Australia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Event-free Survival (time frame: Up to 4 years after study enrollment). The study lists 3 primary outcomes in all. 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 NCT00653068, which also lists 2 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 23 Apr 2024.