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

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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

Tracking Information
First Submitted Date  ICMJE December 7, 2001
First Posted Date  ICMJE January 27, 2003
Results First Submitted Date  ICMJE May 27, 2016
Results First Posted Date  ICMJE March 1, 2017
Last Update Posted Date August 7, 2019
Study Start Date  ICMJE August 2003
Actual Primary Completion Date January 1, 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2017)
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
  • Local Control and Patterns of Failure [ Time Frame: Up to 5 years after completion of study treatment ]
    Documented and analyzed qualitatively and quantitatively.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Observation or Radiation Therapy and/or Chemotherapy and Second Surgery in Treating Children Who Have Undergone Surgery for Ependymoma
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Tumor
  • Central Nervous System Tumor
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Radiation: radiation therapy
  • 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.
    Interventions:
    • Biological: filgrastim
    • Drug: carboplatin
    • Drug: cyclophosphamide
    • Drug: etoposide
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
    • Drug: Mesna
    • Procedure: therapeutic conventional surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 1, 2013)
378
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE March 31, 2016
Actual Primary Completion Date January 1, 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Netherlands,   New Zealand,   Switzerland,   United States
Removed Location Countries Puerto Rico
 
Administrative Information
NCT Number  ICMJE NCT00027846
Other Study ID Numbers  ICMJE ACNS0121
CDR0000069086 ( Other Identifier: Clinical Trials.gov )
NCI-2012-02431 ( Other Identifier: NCI )
COG-ACNS0121 ( Other Identifier: Children's Oncology Group )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Thomas E. Merchant, DO, PhD St. Jude Children's Research Hospital
PRS Account Children's Oncology Group
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP