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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00027846
First received: December 7, 2001
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Analyzed by standard survival methods, including stratified and unstratified logrank tests and Cox regression analysis for assessing the association between outcome and patient and tumor characteristics, and the product-limit (Kaplan-Meier) estimate for estimation of EFS probability.


Secondary Outcome Measures:
  • Overall survival, defined as time to death [ Time Frame: Up to 5 years after completion of study treatment ] [ Designated as safety issue: No ]
    Analyzed by standard survival methods, including stratified and unstratified logrank tests and Cox regression analysis for assessing the association between outcome and patient and tumor characteristics, and the product-limit (Kaplan-Meier) estimate for estimation of OS probability.

  • Rate of gross-total or near-total resection and second surgery after chemotherapy [ Time Frame: At the time of second surgery ] [ Designated as safety issue: No ]
  • EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma under prescribed treatment strategy [ Time Frame: Up to 5 years after completion of study treatment ] [ Designated as safety issue: No ]
    This analysis will be based on a log-rank comparison of EFS estimates in these two groups.

  • Local control and patterns of failure [ Time Frame: Up to 5 years after completion of study treatment ] [ Designated as safety issue: No ]
    Documented and analyzed qualitatively and quantitatively.


Enrollment: 378
Study Start Date: August 2003
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00027846

  Show 165 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Thomas E. Merchant, DO, PhD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00027846     History of Changes
Other Study ID Numbers: ACNS0121, CDR0000069086, NCI-2012-02431, COG-ACNS0121
Study First Received: December 7, 2001
Last Updated: February 26, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
childhood supratentorial ependymoma
newly diagnosed childhood ependymoma
childhood infratentorial ependymoma

Additional relevant MeSH terms:
Ependymoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Carboplatin
Cyclophosphamide
Etoposide
Vincristine
Podophyllotoxin
Lenograstim
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 16, 2014