Observation or Radiation Therapy and/or Chemotherapy and Second Surgery in Treating Children Who Have Undergone Surgery for Ependymoma

Brain Tumor Clinical Trial

Official title:

A Phase II Trial of Conformal Radiation Therapy for Pediatric Patients With Localized Ependymoma, Chemotherapy Prior to Second Surgery for Incompletely Resected Ependymoma and Observation for Completely Resected, Differentiated, Supratentorial Ependymoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00027846
• Other study ID #: ACNS0121
• Secondary ID: CDR0000069086NCI
• Status: Completed
• Phase: Phase 2
• Start date: August 2003
• Est. completion date: March 31, 2016

Study information

• Verified date: January 2017
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy before surgery may shrink the tumor so that it can be removed during surgery.

PURPOSE: Phase II trial to determine the effectiveness of specialized radiation therapy either alone or after chemotherapy and second surgery in treating children who have undergone surgery for localized ependymoma.

Description:

OBJECTIVES:

• Determine the local control and pattern of failure in children with completely resected, differentiated, supratentorial localized ependymoma after initial surgical resection alone.

• Determine the rate of complete resection with second surgery after chemotherapy in patients with initially incompletely resected localized ependymoma.

• Determine the local control and pattern of failure in patients treated with conformal radiotherapy.

• Determine the influence of histologic grade on the time to progression in patients after treatment with conformal radiotherapy.

OUTLINE: This is a multicenter study. Patients are stratified according to extent of prior surgical resection.

• Group 1 (patients with supratentorial differentiated ependymoma who have undergone gross total resection and have no visible residual tumor): Patients undergo observation.

• Group 2 (patients with supratentorial anaplastic ependymoma or infratentorial anaplastic or differentiated ependymoma who have undergone gross total resection or near total resection): Patients undergo conformal radiotherapy to the brain once daily 5 days a week for 6-6½ weeks.

• Group 3 (patients with tumor of any histology or location who have undergone subtotal resection): Patients receive an initial course of chemotherapy comprising vincristine IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second surgery. Patients who have unresectable disease undergo conformal radiotherapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy.

Patients are followed every 4 months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 250-350 patients will be accrued for this study within 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 378
• Est. completion date: March 31, 2016
• Est. primary completion date: January 1, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 21 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed intracranial ependymoma

• Differentiated ependymoma or anaplastic ependymoma

• No primary spinal cord ependymoma, myxopapillary ependymoma, subependymoma, ependymoblastoma, or mixed glioma

• No evidence of noncontiguous spread beyond primary site

• Initial surgical resection within the past 56 days

PATIENT CHARACTERISTICS:

Age:

• 1 to 21

Performance status:

• No restrictions

Life expectancy:

• At least 2 months

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Able to undergo MRI

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Prior or concurrent corticosteroids allowed

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

• More than 1 prior surgery allowed

Other:

• No other prior treatment for ependymoma

Related Conditions & MeSH terms

• Brain Tumor
• Central Nervous System Neoplasms
• Central Nervous System Tumor
• Ependymoma
• Nervous System Neoplasms

Intervention

Biological:
• filgrastim
Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC >1500/µl given subcutaneously or intravenously.

Drug:
• carboplatin
Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patients with BSA <0.45m2 the dose is 12.5 mg/kg/day.
• cyclophosphamide
Given IV (1000mg/m2/day) Day 1 and 2 given as an IV infusion over one hour following carboplatin administration. For patients with BSA<0.45m2 the dose is 33mg/kg/day on Day 1 and 2.
• etoposide
Given orally (50 mg/m2/day) orally once daily on Days 1 through 21. For patients with BSA < 0.45 m2, the dosage is 1.7 mg/kg/day on Days 1 through 21.
• vincristine sulfate
Given IV or orally (1.5mg/m2/day) (maximum dose 2 mg) Day 1 and 8 given as IV bolus. For patients with BSA<0.45m2 the dose is 0.05mg/kg.

Radiation:
• radiation therapy
Given once daily 5 days a week for 6-6½ weeks

Drug:
• Mesna
Mesna (200mg/m2/dose) Day 1 and 2. For patients with BSA<0.45m2 the dose is (7mg/kg/dose). Combine mesna (200mg/m2) with cyclophosphamide and administer intravenously over one hour followed by mesna (200mg/m2) in 375 cc/m2 D5-1/2NS and run intravenously over 3 hours at 125cc/m2/hr. After 3 hour mesna, administer mesna (200 mg/m2/dose) IV over 15 minutes at hour 5.

Procedure:
• therapeutic conventional surgery

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Herston, Brisbane	Queensland
Australia	John Hunter Hospital	Newcastle	New South Wales
Australia	Women's and Children's Hospital	North Adelaide	South Australia
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Prince of Wales Private Hospital	Randwick	New South Wales
Australia	Westmead Institute for Cancer Research at Westmead Hospital	Westmead	New South Wales
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	Children's Hospital of Western Ontario	London	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Netherlands	University Medical Center Groningen	Groningen
New Zealand	Starship Children's Health	Auckland
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
Switzerland	Swiss Pediatric Oncology Group Geneva	Geneva
Switzerland	Swiss Pediatric Oncology Group Lausanne	Lausanne
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Albany Medical Center Hospital	Albany	New York
United States	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas
United States	C.S. Mott Children's Hospital at University of Michigan Medical Center	Ann Arbor	Michigan
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia
United States	Children's Hospital of Austin	Austin	Texas
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine
United States	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama
United States	St. Luke's Mountain States Tumor Institute - Boise	Boise	Idaho
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Floating Hospital for Children at Tufts - New England Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	T.C. Thompson Children's Hospital	Chattanooga	Tennessee
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Columbus Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Children's Medical Center - Dayton	Dayton	Ohio
United States	Children's Hospital Cancer Center	Denver	Colorado
United States	Blank Children's Hospital	Des Moines	Iowa
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	INOVA Fairfax Hospital	Falls Church	Virginia
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut
United States	Hurley Medical Center	Flint	Michigan
United States	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Greenville Hospital System Cancer Center	Greenville	South Carolina
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia
United States	St. Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California
United States	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Children's Hospital Central California	Madera	California
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Miami Children's Hospital	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	Overlook Hospital	Morristown	New Jersey
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	Memorial Sloan - Kettering Cancer Center	New York	New York
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Children's Hospital & Research Center Oakland	Oakland	California
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Children's Hospital	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Hospital and Health Center & Children's Hospital	Portland	Oregon
United States	Naval Medical Center - Portsmouth	Portsmouth	Virginia
United States	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Carilion Cancer Center of Western Virginia	Roanoke	Virginia
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Kaiser Permanente Medical Center - Oakland	Sacramento	California
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	Children's Hospital and Health Center - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Maine Children's Cancer Program at Barbara Bush Children's Hospital	Scarborough	Maine
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Stanford Comprehensive Cancer Center - Stanford	Stanford	California
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	Toledo 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	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina
United States	Tod Children's Hospital	Youngstown	Ohio

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Netherlands,  New Zealand,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free Survival	Event-free survival is calculated from the date of study enrollment to the date of disease progression, disease relapse, occurrence of second neoplasm, or death from any cause. The product-limit (Kaplan-Meier) estimate is for estimation of Event -free survival (EFS) probability at 5 years.	Up to 5 years after completion of study treatment
Secondary	Overall Survival	Overall survival (OS) is measured from the date of study enrollment to the date to death. The product-limit (Kaplan-Meier) estimate is for estimation of OS probability at 5 years.	Up to 5 years after completion of study treatment
Secondary	Rate of Gross-total or Near-total Resection and Second Surgery After Chemotherapy	The Rate Of Gross-Total or Near-Total Resection With Second Surgery After Chemotherapy Treatment.	At the time of second surgery
Secondary	Event-free Survival (EFS)	EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma for the patients who had sub-total resection initially. The event-free survival (EFS) defined as the date of disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, measured from the start date of radiation therapy. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability.	At 5 years since the time of radiation therapy.
Secondary	Event-free Survival (EFS)	EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma for the patients who were treated with radiation therapy only. The event-free survival (EFS) defined as the time to disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, measured from the start of radiation therapy. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability at 5 years.	At 5 years since the time of radiation therapy
Secondary	Local Control and Patterns of Failure	Documented and analyzed qualitatively and quantitatively.	Up to 5 years after completion of study treatment