RATIONALE: 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. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy before surgery may shrink the tumor so that it can be removed during surgery. PURPOSE: Phase II trial to determine the effectiveness of specialized radiation therapy either alone or after chemotherapy and second surgery in treating children who have undergone surgery for localized ependymoma.
OBJECTIVES: * Determine the local control and pattern of failure in children with completely resected, differentiated, supratentorial localized ependymoma after initial surgical resection alone. * Determine the rate of complete resection with second surgery after chemotherapy in patients with initially incompletely resected localized ependymoma. * Determine the local control and pattern of failure in patients treated with conformal radiotherapy. * Determine the influence of histologic grade on the time to progression in patients after treatment with conformal radiotherapy. OUTLINE: This is a multicenter study. Patients are stratified according to extent of prior surgical resection. * Group 1 (patients with supratentorial differentiated ependymoma who have undergone gross total resection and have no visible residual tumor): Patients undergo observation. * Group 2 (patients with supratentorial anaplastic ependymoma or infratentorial anaplastic or differentiated ependymoma who have undergone gross total resection or near total resection): Patients undergo conformal radiotherapy to the brain once daily 5 days a week for 6-6½ weeks. * Group 3 (patients with tumor of any histology or location who have undergone subtotal resection): Patients receive an initial course of chemotherapy comprising vincristine IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second surgery. Patients who have unresectable disease undergo conformal radiotherapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. Patients are followed every 4 months for 3 years, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 250-350 patients will be accrued for this study within 5 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
378
Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC \>1500/μl given subcutaneously or intravenously.
Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patients with BSA \<0.45m2 the dose is 12.5 mg/kg/day.
Given IV (1000mg/m2/day) Day 1 and 2 given as an IV infusion over one hour following carboplatin administration. For patients with BSA\<0.45m2 the dose is 33mg/kg/day on Day 1 and 2.
Given orally (50 mg/m2/day) orally once daily on Days 1 through 21. For patients with BSA \< 0.45 m2, the dosage is 1.7 mg/kg/day on Days 1 through 21.
Given IV or orally (1.5mg/m2/day) (maximum dose 2 mg) Day 1 and 8 given as IV bolus. For patients with BSA\<0.45m2 the dose is 0.05mg/kg.
Given once daily 5 days a week for 6-6½ weeks
Mesna (200mg/m2/dose) Day 1 and 2. For patients with BSA\<0.45m2 the dose is (7mg/kg/dose). Combine mesna (200mg/m2) with cyclophosphamide and administer intravenously over one hour followed by mesna (200mg/m2) in 375 cc/m2 D5-1/2NS and run intravenously over 3 hours at 125cc/m2/hr. After 3 hour mesna, administer mesna (200 mg/m2/dose) IV over 15 minutes at hour 5.
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, United States
Phoenix Children's Hospital
Phoenix, Arizona, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Southern California Permanente Medical Group
Downey, California, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California, United States
Event-free Survival
Event-free survival is calculated from the date of study enrollment to the date of disease progression, disease relapse, occurrence of second neoplasm, or death from any cause. The product-limit (Kaplan-Meier) estimate is for estimation of Event -free survival (EFS) probability at 5 years.
Time frame: Up to 5 years after completion of study treatment
Overall Survival
Overall survival (OS) is measured from the date of study enrollment to the date to death. The product-limit (Kaplan-Meier) estimate is for estimation of OS probability at 5 years.
Time frame: Up to 5 years after completion of study treatment
Rate of Gross-total or Near-total Resection and Second Surgery After Chemotherapy
The Rate Of Gross-Total or Near-Total Resection With Second Surgery After Chemotherapy Treatment.
Time frame: At the time of second surgery
Event-free Survival (EFS)
EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma for the patients who had sub-total resection initially. The event-free survival (EFS) defined as the date of disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, measured from the start date of radiation therapy. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability.
Time frame: At 5 years since the time of radiation therapy.
Event-free Survival (EFS)
EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma for the patients who were treated with radiation therapy only. The event-free survival (EFS) defined as the time to disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, measured from the start of radiation therapy. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability at 5 years.
Time frame: At 5 years since the time of radiation therapy
Local Control and Patterns of Failure
Documented and analyzed qualitatively and quantitatively.
Time frame: Up to 5 years after completion of study treatment
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Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
Long Beach, California, United States
Childrens Hospital Los Angeles
Los Angeles, California, United States
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
Los Angeles, California, United States
Children's Hospital Central California
Madera, California, United States
Children's Hospital & Research Center Oakland
Oakland, California, United States
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