test

Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Younger Patients With Newly Diagnosed Ependymoma

Conditions

Childhood Infratentorial Ependymoma | Childhood Supratentorial Ependymoma | Newly Diagnosed Childhood Ependymoma

Trial Phase

Phase 3

Trial Purpose and Description

Trial Purpose

This randomized phase III trial is studying maintenance chemotherapy to see how well it works compared to observation following induction chemotherapy and radiation therapy in treating young patients with newly diagnosed ependymoma. Drugs used in chemotherapy, such as vincristine sulfate, carboplatin, cyclophosphamide, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving chemotherapy with radiation therapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started.


Trial Description

 

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.

Participation Guidelines

Age:
1 Year - 21 Years
Gender:
Both

Eligibility Criteria


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
corticosteroids
Sponsor:
Children's Oncology Group
 
National Cancer Institute (NCI)
Dates:
March 2010
Last Updated:
August 6, 2014
Study HIC#:

Clinicaltrials.gov ID: NCT01096368