Clinical Trials /

Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma

NCT01096368

Description:

This partially randomized phase III trial is studying maintenance chemotherapy to see how well it works compared to observation following induction chemotherapy and radiation therapy in treating young patients with newly diagnosed ependymoma. Drugs used in chemotherapy, such as vincristine sulfate, carboplatin, cyclophosphamide, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving chemotherapy with radiation therapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started.

Related Conditions:
  • Anaplastic Ependymoma
  • Ependymoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Younger Patients With Newly Diagnosed Ependymoma
  • Official Title: Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients With Newly Diagnosed Ependymoma Ages 1 to 21 Years

Clinical Trial IDs

  • ORG STUDY ID: ACNS0831
  • SECONDARY ID: NCI-2011-02029
  • SECONDARY ID: COG-ACNS0831
  • SECONDARY ID: CDR0000668560
  • SECONDARY ID: U10CA098543
  • NCT ID: NCT01096368

Conditions

  • Childhood Infratentorial Ependymoma
  • Childhood Supratentorial Ependymoma
  • Newly Diagnosed Childhood Ependymoma

Interventions

DrugSynonymsArms
liposomal vincristine sulfateliposomal vincristine, Marqibo, vincristine liposomal, vincristine sulfate liposome injectionArm I (radiotherapy, chemotherapy)
carboplatinCarboplat, CBDCA, JM-8, Paraplat, ParaplatinArm I (radiotherapy, chemotherapy)
cyclophosphamideCPM, CTX, Cytoxan, Endoxan, EndoxanaArm I (radiotherapy, chemotherapy)
etoposideEPEG, VP-16, VP-16-213Arm I (radiotherapy, chemotherapy)
cisplatinCACP, CDDP, CPDD, DDPArm I (radiotherapy, chemotherapy)

Purpose

This randomized phase III trial is studying maintenance chemotherapy to see how well it works compared to observation following induction chemotherapy and radiation therapy in treating young patients with newly diagnosed ependymoma. Drugs used in chemotherapy, such as vincristine sulfate, carboplatin, cyclophosphamide, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving chemotherapy with radiation therapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the event-free survival (EFS) and overall survival (OS) of children with
      completely resected ependymoma treated with maintenance chemotherapy comprising vincristine
      sulfate, cisplatin, etoposide, and cyclophosphamide (VCEC) versus observation following
      post-operative conformal radiotherapy (cRT).

      SECONDARY OBJECTIVES:

      I. To estimate the EFS and OS of children with incompletely resected ependymoma who are
      unable to achieve a complete response (CR) by post-operative induction chemotherapy or by
      second surgery who are non-randomly assigned to cRT followed by VCEC.

      II. To further evaluate the EFS and OS of children with supratentorial classic ependymoma who
      achieve a complete resection at first or second resection or children who achieve a CR to
      short-course induction chemotherapy following first surgery.

      III. To determine the neurologic, neuropsychological, and endocrine long-term sequelae of
      surgery, cRT, and VCEC as compared to those patients treated on COG-ACNS0121.

      IV. To determine biologic prognostic factors in childhood ependymoma by utilizing genomic
      profiles via comparative genomic hybridization and single-nucleotide polymorphism arrays, and
      microarray gene expression profiling analysis on initial tumor samples and correlating this
      with clinical outcome.

      V. To evaluate prognostic immune-function gene expression in ependymomas. VI. To build upon
      the data derived from COG-ACNS0121 to develop genotypically based classification signatures
      and to correlate these to WHO grade, location, extent of resection, treatment, EFS, and OS.

      VII. To evaluate telomere maintenance as a prognostic marker.

      OUTLINE: This is a multicenter study. Patients are stratified according to extent of
      resection at initial surgery (total vs near total resection), tumor histology, and tumor
      location (infratentorial primary tumor vs supratentorial anaplastic tumor). Patients are
      randomized to 1 of 2 treatment arms. Patients with supratentorial classic tumor are assigned
      to arm II.

      All patients receive induction chemotherapy comprising vincristine sulfate IV on days 1 and
      8, carboplatin IV over 15-60 minutes on day 1, and cyclophosphamide IV over 30-60 minutes on
      days 1-2. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of course 2
      only. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or
      unacceptable toxicity. Patients achieving stable disease, partial response, or locally
      progressive disease and who are deemed potentially resectable undergo surgery within 15 days
      after completion of induction chemotherapy.

      ARM I: Patients undergo conformal radiotherapy over 6-7 weeks. Patients then receive
      vincristine sulfate IV on days 1, 8, and 15 (courses 1-3 only); etoposide IV over 1-2 hours
      on days 1-3; cisplatin IV over 1-8 hours on day 1; and cyclophosphamide IV over 30-60 minutes
      on days 1-2. Treatment repeats every 21 days for 4 courses in the absence of disease
      progression or unacceptable toxicity.

      ARM II: Patients undergo conformal radiotherapy over 6-7 weeks. Some patients undergo blood
      and tissue sample collection before treatment and after surgery for gene expression
      microarray, genomic hybridization array, and other correlative studies.

      After completion of study therapy, patients are followed up every 4 months for 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (radiotherapy, chemotherapy)ExperimentalPatients undergo 3-dimensional conformal radiation therapy over 6-7 weeks. Patients then receive liposomal vincristine sulfate IV on days 1, 8, and 15 (courses 1-3 only); etoposide IV over 1-2 hours on days 1-3; carboplatin on day 1, cisplatin IV over 1-8 hours on day 1; cyclophosphamide IV over 30-60 minutes on days 1-2 and filgrastim. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  • liposomal vincristine sulfate
  • carboplatin
  • cyclophosphamide
  • etoposide
  • cisplatin
Arm II (radiotherapy)Active ComparatorPatients undergo 3-dimensional conformal radiation therapy over 6-7 weeks.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically confirmed intracranial ependymoma meeting the following criteria:
    
                   -  Newly diagnosed disease
    
                   -  Classic ependymoma (WHO II) or anaplastic ependymoma (WHO III), including the
                      following subtypes:
    
                        -  Clear cell
    
                        -  Papillary
    
                        -  Cellular
    
                        -  Combination of the above
    
              -  No diagnosis of spinal cord ependymoma, myxopapillary ependymoma, subependymoma,
                 ependymoblastoma, or mixed glioma
    
              -  Has undergone surgical resection of the primary tumor
    
                   -  More than 1 attempted resection allowed
    
              -  No metastatic disease by MRI or cerebrospinal fluid (CSF) cytology
    
                   -  CSR cytology from a ventriculostomy or permanent VP shunt that reveals the
                      presence of tumor cells is indicative of metastatic disease
    
              -  No evidence of non-contiguous spread beyond the primary site as determined by pre- or
                 post-operative MRI of brain, pre- or post-operative MRI of the spine, and
                 post-operative CSF cytology obtained from the lumbar CSF space
    
                   -  Lumbar CSF examination may be waived if deemed to be medically contraindicated
    
              -  ECOG performance status (PS) 0-2
    
                   -  Karnofsky PS for patients > 16 years of age
    
                   -  Lansky PS for patients ≤ 16 years of age
    
              -  ANC ≥ 1,000/μL
    
              -  Platelet count ≥ 100,000/μL (transfusion independent)
    
              -  Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on
                 age/gender as follows:
    
                   -  0.4 mg/dL (1 month to < 6 months of age)
    
                   -  0.5 mg/dL (6 months to < 1 year of age)
    
                   -  0.6 mg/dL (1 to 2 years of age)
    
                   -  0.8 mg/dL (2 to < 6 years of age)
    
                   -  1.0 mg/dL (6 to 10 years of age)
    
                   -  1.2 mg/dL (10 to 13 years of age)
    
                   -  1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
    
                   -  1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
    
              -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 3 times ULN for patients
                 with Gilbert syndrome or hemolytic anemia)
    
              -  AST or ALT < 3 times ULN
    
              -  Adequate cardiac function defined as 1 of the following:
    
                   -  Shortening fraction ≥ 27% by ECHO
    
                   -  Ejection fraction ≥ 50% by gated radionuclide study.
    
              -  Not pregnant or nursing
    
                   -  Patients who agree to stop nursing while on this study are allowed
    
              -  Negative pregnancy test
    
              -  Fertile patients must use effective contraception
    
              -  No prior treatment for ependymoma other than surgical intervention and corticosteroids
          
    Maximum Eligible Age:21 Years
    Minimum Eligible Age:1 Year
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Event-free survival (EFS) defined as time to the first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Using Kaplan-Meier curves to estimate the observed EFS for the two randomization arms (post-radiation Maintenance arm and post-radiation Observation only arm). Log rank tests will be used to compare the observed EFS between the two randomization arms. Stratified log rank test will also be performed to examine the treatment difference with consideration and adjustment for the randomization groups.

    Secondary Outcome Measures

    Measure:EFS and OS of children with incompletely resected ependymoma who are unable to achieve a complete response (CR) by post-operative induction chemotherapy or by second surgery
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Kaplan-Meier curves will be used to estimate the EFS and OS for patients who were non-randomly assigned to receive maintenance chemotherapy after incomplete resection
    Measure:EFS and OS of children with supratentorial classic ependymoma who achieve a complete resection at first or second surgery or children who achieve a CR after induction chemotherapy assigned to observation
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Estimated using Kaplan-Meier curves for patients with supratentorial classic disease that achieve complete resection or CR to induction chemotherapy and are assigned to observation only.
    Measure:Neurologic, neuropsychological, and endocrine long-term sequelae of surgery, conformal radiotherapy, and maintenance chemotherapy
    Time Frame:At 9, 30, and 60 months post diagnosis
    Safety Issue:
    Description:
    Measure:Gene expression signatures and genomic alterations in pediatric ependymoma
    Time Frame:At the time of first or second surgery
    Safety Issue:
    Description:

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Children's Oncology Group

    Last Updated

    September 8, 2017