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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01096368
First received: March 30, 2010
Last updated: August 6, 2014
Last verified: August 2014
  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.


Condition Intervention Phase
Childhood Infratentorial Ependymoma
Childhood Supratentorial Ependymoma
Newly Diagnosed Childhood Ependymoma
Drug: liposomal vincristine sulfate
Other: clinical observation
Radiation: 3-dimensional conformal radiation therapy
Drug: carboplatin
Drug: cyclophosphamide
Drug: etoposide
Drug: cisplatin
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients With Newly Diagnosed Ependymoma Ages 1 to 21 Years

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Overall survival (OS) [ Time Frame: From the time of randomization to death, assessed up to 5 years ] [ Designated as safety issue: No ]
    Using Kaplan-Meier curves to estimate the observed OS 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 OS 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:
  • 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 ] [ Designated as safety issue: No ]
    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

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Neurologic, neuropsychological, and endocrine long-term sequelae of surgery, conformal radiotherapy, and maintenance chemotherapy [ Time Frame: At 9, 30, and 60 months post diagnosis ] [ Designated as safety issue: Yes ]
  • Gene expression signatures and genomic alterations in pediatric ependymoma [ Time Frame: At the time of first or second surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: March 2010
Estimated Primary Completion Date: March 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (radiotherapy, chemotherapy)
Patients 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.
Drug: liposomal vincristine sulfate
Given IV
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection
Radiation: 3-dimensional conformal radiation therapy
Patients undergo conformal radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Other: laboratory biomarker analysis
Optional correlative studies
Active Comparator: Arm II (radiotherapy)
Patients undergo 3-dimensional conformal radiation therapy over 6-7 weeks.
Other: clinical observation
Patients undergo observation
Other Name: observation
Radiation: 3-dimensional conformal radiation therapy
Patients undergo conformal radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Other: laboratory biomarker analysis
Optional correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01096368

Contacts
Contact: Amy A. Smith, MD 321-841-8560 amy.smith@orlandohealth.com

  Show 155 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Amy A. Smith, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01096368     History of Changes
Other Study ID Numbers: ACNS0831, NCI-2011-02029, COG-ACNS0831, CDR0000668560, U10CA098543
Study First Received: March 30, 2010
Last Updated: August 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Ependymoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Carboplatin
Cyclophosphamide
Cisplatin
Etoposide
Vincristine
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
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014