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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00653068
Other study ID # ACNS0333
Secondary ID NCI-2009-00337CD
Status Completed
Phase Phase 3
First received
Last updated
Start date February 10, 2009
Est. completion date March 31, 2024

Study information

Verified date April 2024
Source Children's Oncology Group
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


Description:

PRIMARY OBJECTIVES: I. 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: I. 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.


Recruitment information / eligibility

Status Completed
Enrollment 70
Est. completion date March 31, 2024
Est. primary completion date September 27, 2016
Accepts healthy volunteers No
Gender All
Age group N/A to 21 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Radiation:
3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
Procedure:
Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC rescue
Drug:
Carboplatin
Given IV
Cisplatin
Given IV
Cyclophosphamide
Given IV
Etoposide
Given IV
Biological:
Filgrastim
Given IV or SC
Other:
Laboratory Biomarker Analysis
Correlative studies
Drug:
Leucovorin Calcium
Given IV or PO
Methotrexate
Given IV
Thiotepa
Given IV
Vincristine Sulfate
Given IV

Locations

Country Name City State
Australia Royal Children's Hospital Parkville Victoria
Australia Princess Margaret Hospital for Children Perth Western Australia
Canada Alberta Children's Hospital Calgary Alberta
Canada McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario
Canada Kingston Health Sciences Centre Kingston Ontario
Canada Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec
Canada Hospital for Sick Children Toronto Ontario
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States Mission Hospital Asheville North Carolina
United States Children's Healthcare of Atlanta - Egleston Atlanta Georgia
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States Walter Reed National Military Medical Center Bethesda Maryland
United States Children's Hospital of Alabama Birmingham Alabama
United States University of Alabama at Birmingham Cancer Center Birmingham Alabama
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Montefiore Medical Center - Moses Campus Bronx New York
United States Roswell Park Cancer Institute Buffalo New York
United States UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina
United States Medical University of South Carolina Charleston South Carolina
United States West Virginia University Charleston Division Charleston West Virginia
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
United States Lurie Children's Hospital-Chicago Chicago Illinois
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States Rainbow Babies and Childrens Hospital Cleveland Ohio
United States Prisma Health Richland Hospital Columbia South Carolina
United States Nationwide Children's Hospital Columbus Ohio
United States Driscoll Children's Hospital Corpus Christi Texas
United States Dayton Children's Hospital Dayton Ohio
United States Wayne State University/Karmanos Cancer Institute Detroit Michigan
United States Kaiser Permanente Downey Medical Center Downey California
United States Golisano Children's Hospital of Southwest Florida Fort Myers Florida
United States Lee Memorial Health System Fort Myers Florida
United States Cook Children's Medical Center Fort Worth Texas
United States University of Florida Health Science Center - Gainesville Gainesville Florida
United States BI-LO Charities Children's Cancer Center Greenville South Carolina
United States Greenville Cancer Treatment Center Greenville South Carolina
United States Hackensack University Medical Center Hackensack New Jersey
United States Connecticut Children's Medical Center Hartford Connecticut
United States Penn State Children's Hospital Hershey Pennsylvania
United States University of Hawaii Cancer Center Honolulu Hawaii
United States Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas
United States Riley Hospital for Children Indianapolis Indiana
United States University of Mississippi Medical Center Jackson Mississippi
United States Nemours Children's Clinic-Jacksonville Jacksonville Florida
United States Children's Mercy Hospitals and Clinics Kansas City Missouri
United States East Tennessee Childrens Hospital Knoxville Tennessee
United States University of Kentucky/Markey Cancer Center Lexington Kentucky
United States University of Arkansas for Medical Sciences Little Rock Arkansas
United States Miller Children's and Women's Hospital Long Beach Long Beach California
United States Children's Hospital Los Angeles Los Angeles California
United States Norton Children's Hospital Louisville Kentucky
United States Valley Children's Hospital Madera California
United States Marshfield Medical Center-Marshfield Marshfield Wisconsin
United States Loyola University Medical Center Maywood Illinois
United States University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida
United States Children's Hospital of Wisconsin Milwaukee Wisconsin
United States Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota
United States Morristown Medical Center Morristown New Jersey
United States Children's Hospital New Orleans New Orleans Louisiana
United States Tulane University School of Medicine New Orleans Louisiana
United States Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York
United States Memorial Sloan Kettering Cancer Center New York New York
United States NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York
United States UCSF Benioff Children's Hospital Oakland Oakland California
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Children's Hospital and Medical Center of Omaha Omaha Nebraska
United States Children's Hospital of Orange County Orange California
United States AdventHealth Orlando Orlando Florida
United States Nemours Children's Clinic - Orlando Orlando Florida
United States Orlando Health Cancer Institute Orlando Florida
United States Saint Joseph's Regional Medical Center Paterson New Jersey
United States Nemours Children's Clinic - Pensacola Pensacola Florida
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Rhode Island Hospital Providence Rhode Island
United States Mayo Clinic in Rochester Rochester Minnesota
United States University of Rochester Rochester New York
United States Washington University School of Medicine Saint Louis Missouri
United States Johns Hopkins All Children's Hospital Saint Petersburg Florida
United States Primary Children's Hospital Salt Lake City Utah
United States Methodist Children's Hospital of South Texas San Antonio Texas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States Rady Children's Hospital - San Diego San Diego California
United States UCSF Medical Center-Mission Bay San Francisco California
United States UCSF Medical Center-Parnassus San Francisco California
United States Seattle Children's Hospital Seattle Washington
United States Overlook Hospital Summit New Jersey
United States Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida
United States Mercy Children's Hospital Toledo Ohio
United States New York Medical College Valhalla New York
United States Children's National Medical Center Washington District of Columbia
United States Saint Mary's Hospital West Palm Beach Florida
United States Alfred I duPont Hospital for Children Wilmington Delaware

Sponsors (2)

Lead Sponsor Collaborator
Children's Oncology Group National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. Up to 4 years after study enrollment
Primary 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. Up to 4 years after study enrollment
Primary Toxic Death The number of patients who experience death that is considered to be primarily attributable to complications of treatment. During and after completion of study treatment up to 1 year after enrollment.
Secondary 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. During protocol therapy up to 1 year after enrollment.
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