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

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ClinicalTrials.gov Identifier: NCT01096368
Recruitment Status : Recruiting
First Posted : March 31, 2010
Last Update Posted : October 18, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

March 30, 2010
March 31, 2010
October 18, 2018
March 29, 2010
December 31, 2021   (Final data collection date for primary outcome measure)
  • Event-free survival (EFS) [ Time Frame: From first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause, assessed up to 5 years ]
    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. If outcome data on ACNS0121 or this study suggest a difference or a different pattern in outcome between the 2 randomization strata, the primary analyses will be supplemented with log-rank tests performed separately in each stratum in order not to confound the overall conclusions of the study with respect to the effect of maintenance therapy.
  • Overall survival (OS) [ Time Frame: From the time of randomization to death, assessed up to 5 years ]
    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. If outcome data on ACNS0121 or this study suggest a difference or a different pattern in outcome between the 2 randomization strata, the primary analyses will be supplemented with log-rank tests performed separately in each stratum in order not to confound the overall conclusions of the study with respect to the effect of maintenance therapy.
  • Event-free survival (EFS)
  • Overall survival (OS)
Complete list of historical versions of study NCT01096368 on ClinicalTrials.gov Archive Site
  • Event free survival (EFS) 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 ]
    Kaplan-Meier curves will be used to estimate the EFS for patients who were non-randomly assigned to receive maintenance chemotherapy after incomplete resection
  • Overall survival (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 ]
    Kaplan-Meier curves will be used to estimate the OS for patients who were non-randomly assigned to receive maintenance chemotherapy after incomplete resection
  • Event free survival (EFS) of children with supratentorial classic ependymoma who achieve complete resection at first or second surgery or children who achieve complete response (CR) after induction chemo assigned to observation [ Time Frame: Up to 5 years ]
    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.
  • Overall survival (OS) of children with supratentorial classic ependymoma who achieve complete resection at first or second surgery or children who achieve complete response (CR) after induction chemo assigned to observation [ Time Frame: Up to 5 years ]
    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 ]
    Will be observed.
  • Gene expression signatures and genomic alterations in pediatric ependymoma [ Time Frame: At the time of first or second surgery ]
    Will be observed.
  • Telomere maintenance [ Time Frame: Up to 5 years ]
    Descriptive statistics will be used to summarize the various telomere maintenance measures. Log rank tests and multivariate Cox proportional hazards models will be used to explore the association between a telomere maintenance measurement and EFS/OS, with potential adjustments for the effects of other possible prognostic factors. Reliability of human telomerase reverse transcriptase (hTERT) immunohistochemistry results versus telomeric repeat amplification protocol (TRAP) assay results will be calculated using the kappa statistic.
  • 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
  • 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
  • Neurologic, neuropsychological, and endocrine long-term sequelae of surgery, cRT, and VCEC as compared to those patients treated on COG-ACNS0121
  • Gene expression signatures and genomic alterations in pediatric ependymoma
  • Prognostic molecular signatures and genomic alterations in ependymomas
Not Provided
Not Provided
 
Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma
Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients With Newly Diagnosed Ependymoma Ages 1 to 21 Years
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.

PRIMARY OBJECTIVES:

I. To determine the event free survival (EFS) and overall survival (OS) of children with completely resected ependymoma treated with post-operative conformal radiation therapy (cRT) and then randomized to receive or not receive four cycles of post radiation maintenance chemotherapy (vincristine sulfate [vincristine] cisplatin, etoposide and cyclophosphamide [VCEC]).

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 will then be non-randomly assigned to cRT followed by four cycles of maintenance chemotherapy (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 evaluate whether the addition of maintenance chemotherapy post-radiation therapy contributes to neurobehavioral morbidity and reduced functional outcomes over time, compared to patients treated with radiation therapy followed by observation alone.

IV. To examine differences in neurobehavioral outcomes and quality of life of children treated with proton beam radiation therapy compared to children treated with conventional radiation delivery techniques.

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

VI. Explore prognostic molecular signatures and genomic alterations in ependymomas.

VII. Evaluate prognostic immune-function gene expression in ependymomas. VIII. Build upon the data derived from COG-ACNS0121 to develop genotypically based classification signatures and to correlate these to World Health Organization (WHO) grade, location, extent of resection, treatment, EFS, and OS.

IX. To evaluate telomere maintenance as a prognostic marker.

OUTLINE: Patients are assigned to Arm I or randomized to Arms II or III.

Arm I: Patients receive vincristine sulfate intravenously (IV) over 1 minute on days 1 and 8 of courses 1 and 2, carboplatin IV over 15-60 minutes on day 1 of courses 1 and 2, and cyclophosphamide IV over 30-60 minutes on days 1-2 of course 1 only. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of course 2 only. Course 1 continues for 3 weeks and course 2 continues for 4 weeks in the absence of disease progression or unacceptable toxicity. Patients with complete response are randomized to Arm II or III. 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. Patients with sub total resection are assigned to Arm II. Patients with gross total resection undergo observation.

ARM II: Patients undergo conformal radiotherapy over 6-7 weeks. Patients then receive vincristine sulfate IV on days 1, 8, and 15 of courses 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 courses in the absence of disease progression or unacceptable toxicity.

ARM III: Patients undergo conformal radiotherapy over 6-7 weeks and then undergo observation.

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

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Cellular Ependymoma
  • Childhood Anaplastic Ependymoma
  • Childhood Infratentorial Ependymoma
  • Childhood Supratentorial Ependymoma
  • Clear Cell Ependymoma
  • Ependymoma
  • Newly Diagnosed Childhood Ependymoma
  • Papillary Ependymoma
  • Radiation: 3-Dimensional Conformal Radiation Therapy
    Patients undergo conformal radiotherapy
    Other Names:
    • 3-dimensional radiation therapy
    • 3D CONFORMAL RADIATION THERAPY
    • 3D CRT
    • 3D-CRT
    • Conformal Therapy
    • Radiation Conformal Therapy
  • Drug: Carboplatin
    Given IV
    Other Names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Drug: Cisplatin
    Given IV
    Other Names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum
    • Cis-dichloroammine Platinum (II)
    • Cis-platinous Diamine Dichloride
    • Cis-platinum
    • Cis-platinum II
    • Cis-platinum II Diamine Dichloride
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citoplatino
    • Citosin
    • Cysplatyna
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone's Chloride
    • Peyrone's Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • Other: Clinical Observation
    Patients undergo observation
    Other Name: observation
  • 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
    • Claphene
    • CP monohydrate
    • CTX
    • CYCLO-cell
    • Cycloblastin
    • Cycloblastine
    • Cyclophospham
    • Cyclophosphamid monohydrate
    • Cyclophosphamidum
    • Cyclophosphan
    • Cyclophosphane
    • Cyclophosphanum
    • Cyclostin
    • Cyclostine
    • Cytophosphan
    • Cytophosphane
    • Cytoxan
    • Fosfaseron
    • Genoxal
    • Genuxal
    • Ledoxina
    • Mitoxan
    • Neosar
    • Revimmune
    • Syklofosfamid
    • WR- 138719
  • Drug: Etoposide
    Given IV
    Other Names:
    • Demethyl Epipodophyllotoxin Ethylidine Glucoside
    • EPEG
    • Lastet
    • Toposar
    • Vepesid
    • VP 16-213
    • VP-16
    • VP-16-213
  • Other: Laboratory Biomarker Analysis
    Optional correlative studies
  • Drug: Vincristine Sulfate Liposome
    Given IV
    Other Name: Marqibo
  • Experimental: Arm I (radiotherapy, chemotherapy)
    Patients receive vincristine sulfate IV over 1 minute on days 1 and 8 of courses 1 and 2, carboplatin IV over 15-60 minutes on day 1 of courses 1 and 2, and cyclophosphamide IV over 30-60 minutes on days 1-2 of course 1 only. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of course 2 only. Course 1 continues for 3 weeks and course 2 continues for 4 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Carboplatin
    • Drug: Cyclophosphamide
    • Drug: Etoposide
    • Other: Laboratory Biomarker Analysis
    • Drug: Vincristine Sulfate Liposome
  • Experimental: Arm II (radiotherapy, chemotherapy)
    Patients undergo conformal radiotherapy over 6-7 weeks. Patients then receive vincristine sulfate IV on days 1, 8, and 15 of courses 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 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Radiation: 3-Dimensional Conformal Radiation Therapy
    • Drug: Cisplatin
    • Drug: Cyclophosphamide
    • Drug: Etoposide
    • Other: Laboratory Biomarker Analysis
    • Drug: Vincristine Sulfate Liposome
  • Active Comparator: Arm III (radiotherapy, observation)
    Patients undergo conformal radiotherapy over 6-7 weeks and then undergo observation.
    Interventions:
    • Radiation: 3-Dimensional Conformal Radiation Therapy
    • Other: Clinical Observation
    • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
500
400
Not Provided
December 31, 2021   (Final data collection date for primary outcome measure)

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
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • 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
Sexes Eligible for Study: All
13 Months to 20 Years   (Child, Adult)
No
Australia,   Canada,   New Zealand,   United States
 
 
NCT01096368
ACNS0831
NCI-2011-02029 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COG-ACNS0831
CDR0000668560
10-01676
ACNS0831 ( Other Identifier: Childrens Oncology Group )
ACNS0831 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
No
Not Provided
Not Provided
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Amy Smith Children's Oncology Group
Children's Oncology Group
August 2018

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