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

Children's Oncology Group

Status and phase: Completed; Phase 2

Conditions: Brain Tumor; Central Nervous System Tumor

Treatments: Drug: Mesna; Radiation: radiation therapy; Drug: cyclophosphamide; Drug: vincristine sulfate; Drug: carboplatin; Biological: filgrastim; Drug: etoposide; Procedure: therapeutic conventional surgery

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00027846

ACNS0121

COG-ACNS0121 (Other Identifier)

NCI-2012-02431 (Other Identifier)

CDR0000069086 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 378 patients

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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378 participants in 3 patient groups

GTR1 Differentiated Histology Supratentorial (Group 1)

No Intervention group

Description:

Patients undergo observation.

Radiation (Group 2)

Experimental group

Description:

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.

Treatment:

Radiation: radiation therapy

Sub-Total Resection Any Histology or Location (STR) (Group 3)

Experimental group

Description:

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.

Treatment:

Drug: Mesna

Biological: filgrastim

Radiation: radiation therapy

Drug: vincristine sulfate

Drug: etoposide

Drug: cyclophosphamide

Drug: carboplatin

Procedure: therapeutic conventional surgery