Observation or Radiation Therapy and/or Chemotherapy and Second Surgery in Treating Children Who Have Undergone Surgery for Ependymoma

Phase 2

Completed

• Conditions: Central Nervous System Tumor; Brain Tumor
• Interventions: Radiation: radiation therapy; Biological: filgrastim; Drug: carboplatin; Drug: cyclophosphamide; Drug: etoposide; Drug: vincristine sulfate; Drug: Mesna; Procedure: therapeutic conventional surgery

• Registration Number: NCT00027846
• Lead Sponsor: Children's Oncology Group

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2001-12-07
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Study Start: 2003-08
• Primary Completion: 2010-01-01
• Study Completion: 2016-03-31
• Results First Submitted: 2016-05-27
• Status Verified: 2017-01
• Results First Submitted QC: 2017-01-11
• Results First Posted: 2017-03-01
• Last Update Submitted: 2019-07-24
• Last Update Posted: 2019-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 378

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Radiation (Group 2)	radiation therapy	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.
Sub-Total Resection Any Histology or Location (STR) (Group 3)	filgrastim	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.
Sub-Total Resection Any Histology or Location (STR) (Group 3)	radiation therapy	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.
Sub-Total Resection Any Histology or Location (STR) (Group 3)	vincristine sulfate	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.
Sub-Total Resection Any Histology or Location (STR) (Group 3)	therapeutic conventional surgery	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.
Sub-Total Resection Any Histology or Location (STR) (Group 3)	cyclophosphamide	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.
Sub-Total Resection Any Histology or Location (STR) (Group 3)	carboplatin	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.
Sub-Total Resection Any Histology or Location (STR) (Group 3)	etoposide	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.
Sub-Total Resection Any Histology or Location (STR) (Group 3)	Mesna	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.

Primary Outcome Measures

Name	Time	Method
Event-free Survival	Up to 5 years after completion of study treatment	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Up to 5 years after completion of study treatment	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.
Event-free Survival (EFS)	At 5 years since the time of radiation therapy	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.
Local Control and Patterns of Failure	Up to 5 years after completion of study treatment	Documented and analyzed qualitatively and quantitatively.
Rate of Gross-total or Near-total Resection and Second Surgery After Chemotherapy	At the time of second surgery	The Rate Of Gross-Total or Near-Total Resection With Second Surgery After Chemotherapy Treatment.

Trial Locations

Locations (164)

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

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

Scroll for more (154 remaining)