Purpose

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.

Category

IRB Number
20110258HU
NCT Number
NCT01096368
Open to Enrollment
Yes
Sponsor
Children's Oncology Group -



Study Contact

Principal Investigator
Anne-Marie Langevin

Virginia Diaz
(210) 562-9149
diazvr@uthscsa.edu



Eligibility

Eligible Ages
Between 13 Months and 20 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

    • Patients must be newly diagnosed with histologically confirmed intracranial ependymoma; patients with classic ependymoma (WHO II) or anaplastic ependymoma (WHO III) are eligible, as are various subtypes described as clear cell, papillary, cellular or a combination of the above
    • There is no minimum performance level; children with ependymoma may suffer neurologic sequelae as a result of their tumor or surgical measures taken to establish a diagnosis and resect the tumor; in the majority of cases, there is neurologic recovery; neurologic recovery is not likely to be impeded by protocol therapy
    • REGULATORY: All patients and/or their parents or legal guardians must sign a written informed consent
    • REGULATORY: All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria

    • Patients with evidence of metastatic disease will be excluded; any evidence of non-contiguous spread beyond the primary site as determined by pre or post-operative magnetic resonance (MR) imaging of brain, pre or post-operative MR imaging of the spine, and post-operative cerebrospinal fluid (CSF) cytology obtained from the lumbar CSF space (the requirement for lumbar CSF examination may be waived if deemed to be medically contraindicated); CSF cytology from a ventriculostomy or permanent ventriculoperitoneal (VP) shunt that reveals the presence of tumor cells is indicative of metastatic disease
    • Patients with a diagnosis of spinal cord ependymoma, myxopapillary ependymoma, subependymoma, ependymoblastoma, or mixed glioma are NOT eligible
    • No prior treatment other than surgical intervention and corticosteroids; patients are allowed to have had more than one attempt at resection prior to enrollment
    • Pregnant female patients are not eligible for this study
    • Post-menarchal females may not participate unless a pregnancy test with a negative result has been obtained
    • Males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
    • Lactating females may not participate unless they have agreed not to breastfeed a child while on this study

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Condition
  • Anaplastic Ependymoma
  • Brain Ependymoma
  • Cellular Ependymoma
  • Clear Cell Ependymoma
  • Ependymoma
  • Papillary Ependymoma

    • Arm Groups

    ArmDescriptionIntervention
    Experimental

    Arm II (radiotherapy, chemotherapy)

    		Patients undergo conformal radiotherapy over 6-7 weeks. Patients then receive vincristine IV on days 1, 8, and 15 of cycles 1-3 only, etoposide IV over 60-120 minutes on days 1-3, cisplatin IV over 1-8 hours on day 1, and cyclophosphamide IV over 30-60 minutes on days 2-3. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
  • Radiation: 3-Dimensional Conformal Radiation Therapy

    Patients undergo conformal radiotherapy

    Other names:

    • 3-dimensional radiation therapy
    • 3D Conformal
    • 3D CONFORMAL RADIATION THERAPY
    • 3D CRT
    • 3D-CRT
    • Conformal Therapy
    • Radiation Conformal Therapy
    • Radiation, 3D Conformal

  • Drug: Cisplatin

    Given IV

    Other names:

    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum

  • Drug: Cyclophosphamide

    Given IV

    Other names:

    • (-)-Cyclophosphamide
    • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    • Carloxan
    • Ciclofosfamida
    • Ciclofosfamide
    • Cicloxal
    • Clafen <

  • Other: Laboratory Biomarker Analysis

    Optional correlative studies

  • Drug: Etoposide

    Given IV

    Other names:

    • Demethyl Epipodophyllotoxin Ethylidine Glucoside
    • EPEG
    • Lastet
    • Toposar
    • Vepesid
    • VP 16
    • VP 16-213
    • VP-16
    • VP-16-213
    • VP16

  • Drug: Vincristine

    Given IV

    Other names:

    • Leurocristine
    • VCR
    • Vincrystine

    • Experimental

    Arm I (radiotherapy, chemotherapy)

    		Patients receive vincristine IV over 1 minute on days 1 and 8 of cycles 1 and 2, carboplatin IV over 15-60 minutes on day 1 of cycles 1 and 2, and cyclophosphamide IV over 30-60 minutes on days 1-2 of cycle 1 only. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of cycle 2 only. Cycle 1 continues for 3 weeks and cycle 2 continues for 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Drug: Cyclophosphamide

    Given IV

    Other names:

    • (-)-Cyclophosphamide
    • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    • Carloxan
    • Ciclofosfamida
    • Ciclofosfamide
    • Cicloxal
    • Clafen <

  • Other: Laboratory Biomarker Analysis

    Optional correlative studies

  • Drug: Carboplatin

    Given IV

    Other names:

    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carboplatinum
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Nov

  • Drug: Etoposide

    Given IV

    Other names:

    • Demethyl Epipodophyllotoxin Ethylidine Glucoside
    • EPEG
    • Lastet
    • Toposar
    • Vepesid
    • VP 16
    • VP 16-213
    • VP-16
    • VP-16-213
    • VP16

  • Drug: Vincristine

    Given IV

    Other names:

    • Leurocristine
    • VCR
    • Vincrystine

    • Active Comparator

    Arm III (radiotherapy, observation)

    		Patients undergo conformal radiotherapy over 6-7 weeks and then undergo observation.
  • Radiation: 3-Dimensional Conformal Radiation Therapy

    Patients undergo conformal radiotherapy

    Other names:

    • 3-dimensional radiation therapy
    • 3D Conformal
    • 3D CONFORMAL RADIATION THERAPY
    • 3D CRT
    • 3D-CRT
    • Conformal Therapy
    • Radiation Conformal Therapy
    • Radiation, 3D Conformal

  • Other: Laboratory Biomarker Analysis

    Optional correlative studies

  • Other: Clinical Observation

    Patients undergo observation

    Other names:

    • observation

    •