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

Trial Information

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

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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.