Overview

This trial is active, not recruiting.

Conditions brain tumor, central nervous system tumor
Treatments filgrastim, carboplatin, cyclophosphamide, etoposide, vincristine sulfate, radiation therapy, mesna, therapeutic conventional surgery
Phase phase 2
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date August 2003
End date January 2010
Trial size 378 participants
Trial identifier NCT00027846, ACNS0121, CDR0000069086, COG-ACNS0121, NCI-2012-02431

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(No Intervention)
Patients undergo observation.
(Experimental)
Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks.
radiation therapy irradiation, radiotherapy, therapy, radiation
Given once daily 5 days a week for 6-6½ weeks
(Experimental)
Patients receive an initial course of chemotherapy comprising vincristine sulfate 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 sulfate 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 therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy.
filgrastim G CSF, G-CSF, granulocyte colony stimulating factor, granulocyte colony-stimulating factor
Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC >1500/μl given subcutaneously or intravenously.
carboplatin Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA,
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.
cyclophosphamide Neosar, Procytox, Sendoxan, Syklofosfamid, WR-138719, Zytoxan
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.
etoposide Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, epipodophyllotoxin, Lastet, Toposar, VePesid
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.
vincristine sulfate 22-oxovincaleukoblastine, 57-22-7, leurocristine sulfate, VCR, Vincasar PFS
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.
radiation therapy irradiation, radiotherapy, therapy, radiation
Given once daily 5 days a week for 6-6½ weeks
mesna
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.
therapeutic conventional surgery

Primary Outcomes

Measure
Event-free survival, defined as time to disease progression, disease relapse, occurrence of second neoplasm, or death from any cause
time frame: Up to 5 years after completion of study treatment

Secondary Outcomes

Measure
Overall survival, defined as time to death
time frame: Up to 5 years after completion of study treatment
Rate of gross-total or near-total resection and second surgery after chemotherapy
time frame: At the time of second surgery
EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma under prescribed treatment strategy
time frame: Up to 5 years after completion of study treatment
Local control and patterns of failure
time frame: Up to 5 years after completion of study treatment

Eligibility Criteria

Male or female participants from 1 year up to 21 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed intracranial ependymoma - Differentiated ependymoma or anaplastic ependymoma - No primary spinal cord ependymoma, myxopapillary ependymoma, subependymoma, ependymoblastoma, or mixed glioma - No evidence of noncontiguous spread beyond primary site - Initial surgical resection within the past 56 days PATIENT CHARACTERISTICS: Age: - 1 to 21 Performance status: - No restrictions Life expectancy: - At least 2 months Hematopoietic: - Not specified Hepatic: - Not specified Renal: - Not specified Other: - Able to undergo MRI - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: - Not specified Chemotherapy: - No prior chemotherapy Endocrine therapy: - Prior or concurrent corticosteroids allowed Radiotherapy: - No prior radiotherapy Surgery: - See Disease Characteristics - More than 1 prior surgery allowed Other: - No other prior treatment for ependymoma

Additional Information

Official title A Phase II Trial of Conformal Radiation Therapy for Pediatric Patients With Localized Ependymoma, Chemotherapy Prior to Second Surgery for Incompletely Resected Ependymoma and Observation for Completely Resected, Differentiated, Supratentorial Ependymoma
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Children's Oncology Group.