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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00027846
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : March 1, 2017
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Description
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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.


Condition or disease Intervention/treatment Phase
Brain Tumor Central Nervous System Tumor Biological: filgrastim Drug: carboplatin Drug: cyclophosphamide Drug: etoposide Drug: vincristine sulfate Radiation: radiation therapy Drug: Mesna Procedure: therapeutic conventional surgery Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 378 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : August 2003
Actual Primary Completion Date : January 1, 2010
Actual Study Completion Date : March 31, 2016

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
No Intervention: GTR1 Differentiated Histology Supratentorial (Group 1)
Patients undergo observation.
Experimental: Radiation (Group 2)
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: radiation therapy
Given once daily 5 days a week for 6-6½ weeks
Other Name: irradiation, radiotherapy, therapy, radiation
Experimental: Sub-Total Resection Any Histology or Location (STR) (Group 3)
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.
 Biological: filgrastim
Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC >1500/μl given subcutaneously or intravenously.
Other Name: G CSF, G-CSF, granulocyte colony stimulating factor, granulocyte colony-stimulating factor

Drug: carboplatin
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.
Other Name: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA,

Drug: cyclophosphamide
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.
Other Name: Neosar, Procytox, Sendoxan, Syklofosfamid, WR-138719, Zytoxan

Drug: etoposide
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.
Other Name: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, epipodophyllotoxin, Lastet, Toposar, VePesid

Drug: vincristine sulfate
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.
Other Name: 22-oxovincaleukoblastine, 57-22-7, leurocristine sulfate, VCR, Vincasar PFS

Radiation: radiation therapy
Given once daily 5 days a week for 6-6½ weeks
Other Name: irradiation, radiotherapy, therapy, radiation

Drug: 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.

Procedure: therapeutic conventional surgery


Outcome Measures
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Primary Outcome Measures :
  1. Event-free Survival [ Time Frame: 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 :
  1. Overall Survival [ Time Frame: 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.

  2. Rate of Gross-total or Near-total Resection and Second Surgery After Chemotherapy [ Time Frame: At the time of second surgery ]
    The Rate Of Gross-Total or Near-Total Resection With Second Surgery After Chemotherapy Treatment.

  3. Event-free Survival (EFS) [ Time Frame: At 5 years since the time of radiation therapy. ]
    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.

  4. Event-free Survival (EFS) [ Time Frame: 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.

  5. Local Control and Patterns of Failure [ Time Frame: Up to 5 years after completion of study treatment ]
    Documented and analyzed qualitatively and quantitatively.


Eligibility Criteria
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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00027846


Locations
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Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Study Chair: Thomas E. Merchant, DO, PhD St. Jude Children's Research Hospital
More Information
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Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00027846    
Other Study ID Numbers: ACNS0121
CDR0000069086 ( Other Identifier: Clinical Trials.gov )
NCI-2012-02431 ( Other Identifier: NCI )
COG-ACNS0121 ( Other Identifier: Children's Oncology Group )
First Posted: January 27, 2003    Key Record Dates
Results First Posted: March 1, 2017
Last Update Posted: August 7, 2019
Last Verified: January 2017
Keywords provided by Children's Oncology Group:
childhood supratentorial ependymoma
newly diagnosed childhood ependymoma
childhood infratentorial ependymoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Ependymoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Carboplatin
 Etoposide
Vincristine
Podophyllotoxin
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors