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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

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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



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