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

Childhood Atypical Teratoid/Rhabdoid Tumor Clinical Trial

Official title:

Treatment of Atypical Teratoid/Rhabdoid Tumors (AT/RT) of the Central Nervous System With Surgery, Intensive Chemotherapy, and 3-D Conformal Radiation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00653068
• Other study ID #: ACNS0333
• Secondary ID: NCI-2009-00337CD
• Status: Completed
• Phase: Phase 3
• 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
• 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

Related Conditions & MeSH terms

• Childhood Atypical Teratoid/Rhabdoid Tumor
• Rhabdoid Tumor

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.

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive