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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01096368




Registration number
NCT01096368
Ethics application status
Date submitted
30/03/2010
Date registered
31/03/2010
Date last updated
22/11/2023

Titles & IDs
Public title
Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma
Scientific title
Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients With Newly Diagnosed Ependymoma Ages 1 to 21 Years
Secondary ID [1] 0 0
NCI-2011-02029
Secondary ID [2] 0 0
ACNS0831
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaplastic Ependymoma 0 0
Brain Ependymoma 0 0
Cellular Ependymoma 0 0
Clear Cell Ependymoma 0 0
Ependymoma 0 0
Papillary Ependymoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - 3-Dimensional Conformal Radiation Therapy
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cisplatin
Other interventions - Clinical Observation
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Etoposide
Other interventions - Filgrastim
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Mesna
Treatment: Drugs - Vincristine

Experimental: Arm I (chemotherapy, observation) - Patients with classic histology(WHO Grade II) supratentorial ependymoma who have undergone microscopic gross total resection (GTR1) or achieved CR either after first or second resection or after post-operative induction chemotherapy are assigned to observation. For patients without GTR1, induction chemotherapy is comprised of vincristine intravenously (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.

Experimental: Arm II (radiotherapy, chemotherapy) - Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of 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 courses in the absence of disease progression or unacceptable toxicity. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.

Active Comparator: Arm III (radiotherapy, observation) - Patients with supratentorial ependymoma (Grade II without GTR1 or ST Grade III) or any infratentorial ependymoma (Grade II or III) who have undergone gross or near total resection or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks and then undergo observation. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.

Active Comparator: ARM IV (radiotherapy, chemotherapy) - Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.


Treatment: Other: 3-Dimensional Conformal Radiation Therapy
Patients undergo conformal radiotherapy

Treatment: Drugs: Carboplatin
Given IV

Treatment: Drugs: Cisplatin
Given IV

Other interventions: Clinical Observation
Patients undergo observation

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Etoposide
Given IV

Other interventions: Filgrastim
Given SC or IV

Other interventions: Laboratory Biomarker Analysis
Optional correlative studies

Treatment: Drugs: Mesna
Given IV

Treatment: Drugs: Vincristine
Given IV
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival (EFS) in Children Who Have Completely Resected Ependymoma or Achieved CR and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only
Timepoint [1] 0 0
Up to 10 years after enrollment. 5-year estimates of EFS are presented
Primary outcome [2] 0 0
Overall Survival (OS) in Children Who Have Completely Resected Ependymoma or Achieved CR and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only
Timepoint [2] 0 0
Up to 10 years after enrollment. 5-year estimates of OS are presented.

Eligibility
Key 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
Minimum age
12 Months
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/05/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
22/09/2024
Actual
Sample size
Target
Accrual to date
Final
479
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [6] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [7] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [8] 0 0
Monash Medical Center-Clayton Campus - Clayton
Recruitment hospital [9] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [10] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [11] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
5006 - North Adelaide
Recruitment postcode(s) [7] 0 0
3168 - Clayton
Recruitment postcode(s) [8] 0 0
3052 - Parkville
Recruitment postcode(s) [9] 0 0
6008 - Perth
Recruitment postcode(s) [10] 0 0
6009 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Idaho
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Illinois
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Indiana
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Iowa
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Kentucky
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Louisiana
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Michigan
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New Hampshire
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New Mexico
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Vermont
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Virginia
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Washington
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West Virginia
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Wisconsin
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Alberta
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British Columbia
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Manitoba
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Newfoundland and Labrador
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Nova Scotia
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Ontario
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Quebec
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Saskatchewan
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New Zealand
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Auckland
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New Zealand
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Christchurch

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The primary aim of this randomized phase III trial was to study whether the addition of
maintenance chemotherapy delivered after surgical resection and focal radiation would be
better than surgery and focal radiation alone. The trial also studied if patients who
received induction chemotherapy and then either achieved a complete response or went on to
have a complete resection would also benefit from maintenance chemotherapy. Children ages
1-21 years with newly diagnosed intracranial ependymoma were included. There were 2 arms that
were not randomized. One arm studied patients with Grade II tumors located in the
supratentorial compartment that were completely resected. One arm studied patients with
residual tumor and those patients all received maintenance chemotherapy after focal
radiation. Chemotherapy drugs, 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 in combination with radiation therapy may kill more
tumor cells and allow doctors to save the part of the body where the cancer started.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01096368
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Amy A Smith
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01096368