Know Cancer

forgot password

Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients With Newly Diagnosed Ependymoma Ages 1 to 21 Years

Phase 3
1 Year
21 Years
Open (Enrolling)
Childhood Infratentorial Ependymoma, Childhood Supratentorial Ependymoma, Newly Diagnosed Childhood Ependymoma

Thank you

Trial Information

Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients With Newly Diagnosed Ependymoma Ages 1 to 21 Years


I. To determine the event-free survival (EFS) and overall survival (OS) of children with
completely resected ependymoma treated with maintenance chemotherapy comprising vincristine
sulfate, cisplatin, etoposide, and cyclophosphamide (VCEC) versus observation following
post-operative conformal radiotherapy (cRT).


I. To estimate the EFS and OS of children with incompletely resected ependymoma who are
unable to achieve a complete response (CR) by post-operative induction chemotherapy or by
second surgery who are non-randomly assigned to cRT followed by VCEC.

II. To further evaluate the EFS and OS of children with supratentorial classic ependymoma
who achieve a complete resection at first or second resection or children who achieve a CR
to short-course induction chemotherapy following first surgery.

III. To determine the neurologic, neuropsychological, and endocrine long-term sequelae of
surgery, cRT, and VCEC as compared to those patients treated on COG-ACNS0121.

IV. To determine biologic prognostic factors in childhood ependymoma by utilizing genomic
profiles via comparative genomic hybridization and single-nucleotide polymorphism arrays,
and microarray gene expression profiling analysis on initial tumor samples and correlating
this with clinical outcome.

V. To evaluate prognostic immune-function gene expression in ependymomas. VI. To build upon
the data derived from COG-ACNS0121 to develop genotypically based classification signatures
and to correlate these to WHO grade, location, extent of resection, treatment, EFS, and OS.

VII. To evaluate telomere maintenance as a prognostic marker.

OUTLINE: This is a multicenter study. Patients are stratified according to extent of
resection at initial surgery (total vs near total resection), tumor histology, and tumor
location (infratentorial primary tumor vs supratentorial anaplastic tumor). Patients are
randomized to 1 of 2 treatment arms. Patients with supratentorial classic tumor are assigned
to arm II.

All patients receive induction chemotherapy comprising vincristine sulfate IV on days 1 and
8, carboplatin IV over 15-60 minutes on day 1, and cyclophosphamide IV over 30-60 minutes on
days 1-2. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of course 2
only. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or
unacceptable toxicity. Patients achieving stable disease, partial response, or locally
progressive disease and who are deemed potentially resectable undergo surgery within 15 days
after completion of induction chemotherapy.

ARM I: Patients undergo conformal radiotherapy over 6-7 weeks. Patients then receive
vincristine sulfate IV on days 1, 8, and 15 (courses 1-3 only); etoposide IV over 1-2 hours
on days 1-3; cisplatin IV over 1-8 hours on day 1; and cyclophosphamide IV over 30-60
minutes on days 1-2. Treatment repeats every 21 days for 4 courses in the absence of disease
progression or unacceptable toxicity.

ARM II: Patients undergo conformal radiotherapy over 6-7 weeks. Some patients undergo blood
and tissue sample collection before treatment and after surgery for gene expression
microarray, genomic hybridization array, and other correlative studies.

After completion of study therapy, patients are followed up every 4 months for 5 years.

Inclusion Criteria:

- Histologically confirmed intracranial ependymoma meeting the following criteria:

- Newly diagnosed disease

- Classic ependymoma (WHO II) or anaplastic ependymoma (WHO III), including the
following subtypes:

- Clear cell

- Papillary

- Cellular

- Combination of the above

- No diagnosis of spinal cord ependymoma, myxopapillary ependymoma, subependymoma,
ependymoblastoma, or mixed glioma

- Has undergone surgical resection of the primary tumor

- More than 1 attempted resection allowed

- No metastatic disease by MRI or cerebrospinal fluid (CSF) cytology

- CSR cytology from a ventriculostomy or permanent VP shunt that reveals the
presence of tumor cells is indicative of metastatic disease

- No evidence of non-contiguous spread beyond the primary site as determined by pre- or
post-operative MRI of brain, pre- or post-operative MRI of the spine, and
post-operative CSF cytology obtained from the lumbar CSF space

- Lumbar CSF examination may be waived if deemed to be medically contraindicated

- ECOG performance status (PS) 0-2

- Karnofsky PS for patients > 16 years of age

- Lansky PS for patients ≤ 16 years of age

- ANC ≥ 1,000/μL

- Platelet count ≥ 100,000/μL (transfusion independent)

- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on
age/gender as follows:

- 0.4 mg/dL (1 month to < 6 months of age)

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 to 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to 10 years of age)

- 1.2 mg/dL (10 to 13 years of age)

- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 3 times ULN for patients
with Gilbert syndrome or hemolytic anemia)

- AST or ALT < 3 times ULN

- Adequate cardiac function defined as 1 of the following:

- Shortening fraction ≥ 27% by ECHO

- Ejection fraction ≥ 50% by gated radionuclide study.

- Not pregnant or nursing

- Patients who agree to stop nursing while on this study are allowed

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior treatment for ependymoma other than surgical intervention and

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival (EFS) defined as time to the first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause

Outcome Description:

Using Kaplan-Meier curves to estimate the observed EFS for the two randomization arms (post-radiation Maintenance arm and post-radiation Observation only arm). Log rank tests will be used to compare the observed EFS between the two randomization arms. Stratified log rank test will also be performed to examine the treatment difference with consideration and adjustment for the randomization groups.

Outcome Time Frame:

Up to 5 years

Safety Issue:


Principal Investigator

Amy Smith

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

March 2010

Completion Date:

Related Keywords:

  • Childhood Infratentorial Ependymoma
  • Childhood Supratentorial Ependymoma
  • Newly Diagnosed Childhood Ependymoma
  • Ependymoma



Baylor College of Medicine Houston, Texas  77030
Johns Hopkins University Baltimore, Maryland  21205
Memorial Sloan Kettering Cancer Center New York, New York  10021
Cleveland Clinic Foundation Cleveland, Ohio  44195
Roswell Park Cancer Institute Buffalo, New York  14263
Mayo Clinic Rochester, Minnesota  55905
Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
Washington University School of Medicine Saint Louis, Missouri  63110
Hurley Medical Center Flint, Michigan  48503
Medical City Dallas Hospital Dallas, Texas  75230
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Midwest Children's Cancer Center Milwaukee, Wisconsin  53226
Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Loyola University Medical Center Maywood, Illinois  60153
Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114
Morristown Memorial Hospital Morristown, New Jersey  07962-1956
Marshfield Clinic Marshfield, Wisconsin  54449
Loma Linda University Medical Center Loma Linda, California  92354
Newark Beth Israel Medical Center Newark, New Jersey  07112
New York Medical College Valhalla, New York  10595
Dana-Farber Cancer Institute Boston, Massachusetts  02115
Cedars-Sinai Medical Center Los Angeles, California  90048
University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
Madigan Army Medical Center Tacoma, Washington  98431-5048
University of Nebraska Medical Center Omaha, Nebraska  68198-3330
Hackensack University Medical Center Hackensack, New Jersey  07601
Children's Hospital Los Angeles Los Angeles, California  90027-0700
Children's National Medical Center Washington, District of Columbia  20010-2970
All Children's Hospital St. Petersburg, Florida  33701
Advocate Hope Children's Hospital Oak Lawn, Illinois  60453
Saint Jude Midwest Affiliate Peoria, Illinois  61637
Carolinas Medical Center Charlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma  73104
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Driscoll Children's Hospital Corpus Christi, Texas  78466
Scott and White Memorial Hospital Temple, Texas  76508
Southern California Permanente Medical Group Downey, California  90242
Children's Hospital Central California Madera, California  93638-8762
Kosair Children's Hospital Louisville, Kentucky  40202-3830
Children's Hospital Medical Center of Akron Akron, Ohio  44308
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001
Overlook Hospital Summit, New Jersey  07902-0220
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Methodist Children's Hospital of South Texas San Antonio, Texas  78229-3993
Primary Children's Medical Center Salt Lake City, Utah  84113-1100
Montefiore Medical Center Bronx, New York  10467-2490
Rady Children's Hospital - San Diego San Diego, California  92123-4282
Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis, Minnesota  55404
University of New Mexico Cancer Center Albuquerque, New Mexico  87131-5636
Nationwide Children's Hospital Columbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania  15213
Dell Children's Medical Center of Central Texas Austin, Texas  78723
Children's Hospital and Research Center at Oakland Oakland, California  94609-1809
Mary Bridge Children's Hospital and Health Center Tacoma, Washington  98415-0299
Lehigh Valley Hospital - Muhlenberg Bethlehem, Pennsylvania  18017
Presbyterian Hospital Charlotte, North Carolina  28233-3549
Lee Memorial Health System Fort Myers, Florida  33902
University of Alabama at Birmingham Birmingham, Alabama  35294-3300
Children's Hospital of Alabama Birmingham, Alabama  35233
Connecticut Children's Medical Center Hartford, Connecticut  06106
University of North Carolina Chapel Hill, North Carolina  27599
University of Florida Gainesville, Florida  32610-0277
University of Rochester Rochester, New York  14642
Nemours Children's Clinic - Pensacola Pensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum Health Grand Rapids, Michigan  49503
Yale University New Haven, Connecticut  06520
Wayne State University Detroit, Michigan  48202
Mercy Children's Hospital Toledo, Ohio  43608
Legacy Emanuel Children's Hospital Portland, Oregon  97227
BI-LO Charities Children's Cancer Center Greenville, South Carolina  29605
Dartmouth Hitchcock Medical Center Lebanon, New Hampshire  03756
University of Kentucky Lexington, Kentucky  40536-0098
Virginia Commonwealth University Richmond, Virginia  
Florida Hospital Orlando, Florida  32803
Memorial Health University Medical Center Savannah, Georgia  31404
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
Seattle Children's Hospital Seattle, Washington  98105
Wake Forest University Health Sciences Winston-Salem, North Carolina  27157
Childrens Memorial Hospital Chicago, Illinois  60614
Kaiser Permanente-Oakland Oakland, California  94611
M D Anderson Cancer Center- Orlando Orlando, Florida  32806
Saint Luke's Mountain States Tumor Institute Boise, Idaho  83712
Saint Vincent Hospital and Health Services Indianapolis, Indiana  46260
Saint John Hospital and Medical Center Detroit, Michigan  48236
Michigan State University - Breslin Cancer Center East Lansing, Michigan  48824-1313
Saint John's Mercy Medical Center Saint Louis, Missouri  63141
Nevada Cancer Research Foundation CCOP Las Vegas, Nevada  89106
Saint Barnabas Medical Center Livingston, New Jersey  07039
New York University Langone Medical Center New York, New York  10016
Columbia University Medical Center New York, New York  10032
State University of New York Upstate Medical University Syracuse, New York  13210
Saint Vincent Hospital Green Bay, Wisconsin  54301
University of Maryland Greenebaum Cancer Center Baltimore, Maryland  21201
University of Illinois Chicago, Illinois  60612
Cook Children's Medical Center Fort Worth, Texas  76104
Memorial Healthcare System - Joe DiMaggio Children's Hospital Hollywood, Florida  33021
West Virginia University Charleston Charleston, West Virginia  25304
The Children's Medical Center of Dayton Dayton, Ohio  45404
University of Miami Miller School of Medicine-Sylvester Cancer Center Miami, Florida  33136
University of Minnesota Medical Center-Fairview Minneapolis, Minnesota  55455
C S Mott Children's Hospital Ann Arbor, Michigan  48109
Southern Illinois University Springfield, Illinois  62702
Walter Reed National Military Medical Center Bethesda, Maryland  20889
Riley Hospital for Children Indianapolis, Indiana  46202
Cardinal Glennon Children's Medical Center St. Louis, Missouri  63104
UMDNJ - Robert Wood Johnson University Hospital New Brunswick, New Jersey  08903
Miller Children's Hospital Long Beach, California  90806
Childrens Hospital of Orange County Orange, California  92868-3874
Alfred I duPont Hospital for Children Wilmington, Delaware  19803
Nemours Children's Clinic - Jacksonville Jacksonville, Florida  32207-8426
Nemours Childrens Clinic - Orlando Orlando, Florida  32806
Saint Joseph Children's Hospital of Tampa Tampa, Florida  33607
Children's Healthcare of Atlanta - Egleston Atlanta, Georgia  30322
The Childrens Mercy Hospital Kansas City, Missouri  64108
Rainbow Babies and Childrens Hospital Cleveland, Ohio  44106
Penn State Hershey Children's Hospital Hershey, Pennsylvania  17033
Palmetto Health Richland Columbia, South Carolina  29203
East Tennessee Childrens Hospital Knoxville, Tennessee  37916
Saint Mary's Hospital West Palm Beach, Florida  33407
Children's Hospital and Medical Center of Omaha Omaha, Nebraska  68114
Saint Joseph's Regional Medical Center Paterson, New Jersey  07503
Childrens Hospital-King's Daughters Norfolk, Virginia  23507
Children's Hospital Colorado Aurora, Colorado  80045
Lucile Packard Children's Hospital Stanford University Palo Alto, California  94304
University of California San Francisco Medical Center-Parnassus San Francisco, California  94143
Raymond Blank Children's Hospital Des Moines, Iowa  50309
Children's Hospital-Main Campus New Orleans, Louisiana  70118
Saint Christopher's Hospital for Children Philadelphia, Pennsylvania  19134
Greenville Cancer Treatment Center Greenville, South Carolina  29605
Carilion Clinic Children's Hospital Roanoke, Virginia  24014
Providence Sacred Heart Medical Center and Children's Hospital Spokane, Washington  99204
Broward Health Medical Center Fort Lauderdale, Florida  33316
The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park, New York  11040