Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients With Newly Diagnosed Ependymoma Ages 1 to 21 Years
Trial status: Open for Enrollment
Why is this study being done?
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.
Who is eligible to participate?
- 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
- 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