- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02125786
A Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
A Phase II Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
The primary purpose of this study is to investigate whether surgery and re-irradiation will help treat ependymoma that has come back after initial treatment. The combined doses of the first and second courses of radiation are higher than what is usual standard of care. The investigators will study the effects and side effects of surgery and re-irradiation. They will also evaluate and study tumor tissue and blood to learn more about the tumor and how it does or does not respond to treatments and will use magnetic resonance imaging (MRI) and positron emission tomography (PET) scans to see if they can predict tumor response and tumor recurrence.
Participants will be followed for up to 5 years following enrollment. Evaluations during radiation therapy will be done weekly while receiving therapy for up to 7 weeks. Other evaluations will be done at enrollment, every 4 months from enrollment through 3 years, and every 6 months during the 4th and 5th year.
Study Overview
Status
Conditions
Detailed Description
Stratification for treatment will be determined when radiation therapy planning is initiated. Patients will be stratified for outcome according to diagnosis and prior therapy.
- Stratum 1 (initial pattern of failure is local); disease confined to primary site; age >12 months at time of enrollment to < 21 years. Treatment: focal irradiation.
- Stratum 2 (initial pattern of failure is metastatic); neuraxis metastatic disease without equivocal evidence of local failure; age > 36 months at time of enrollment to < 21 years. Treatment: craniospinal irradiation.
- Stratum 3 (Initial pattern of failure is both local and metastatic): neuraxis metastatic disease with unequivocal evidence of local failure; age > 36 months at time of enrollment to < 21 years. Treatment: craniospinal irradiation.
- Stratum 4 (initial pattern of failure is local): disease confined to primary site, age >36 months at time of enrollment to <21 years; tumor shows presence of 1g gain. Treatment: craniospinal irradiation (optional).
PRIMARY OBJECTIVE:
- To prospectively estimate the progression-free and overall survival distributions for children and young adults with recurrent ependymoma treated with a second course of irradiation while monitoring for excessive central nervous system necrosis.
SECONDARY OBJECTIVES:
- To explore potential associations of clinical and treatment factors with the incidence and severity of neurological, endocrine and cognitive deficits in children and young adults with ependymoma treated with a second course of irradiation.
- Using specific measures of sleep quality, excessive daytime sleepiness, daytime activity, fatigue, symptom distress, and quality of life, explore associations of sleep, fatigue and quality of life with other measures of CNS effects, clinical and treatment factors in children and young adults with ependymoma treated with a second course of irradiation.
- To evaluate and explore differences in physical performance and movement in children and young adults with ependymoma treated with a second course of irradiation.
- Estimate and compare the response of residual tumor and the incidence and severity of structural, physiological, and vascular effects of normal brain in children and young adults with ependymoma after treatment with a second course of irradiation using specific methods of diffusion, contrast-enhancement, magnetization transfer, vascular and functional neuroimaging, and explore the association between these and other measures of CNS effects and clinical and treatment factors. Determine the time course of gray matter and white matter tract injury and recovery post irradiation and the association between imaging metrics derived from serial quantitative neural imaging and radiation dosimetry as well as neuro-cognitive outcomes.
Other Pre-Specified (Exploratory) Objectives:
- Estimate the avidity of ependymoma to 18F-fluorodeoxyglucose (FDG) and 11C-methionine positron emission tomography (IND # 104987) prior to radiation therapy and correlate change in avidity 12, 24 and 36 months after a second course of irradiation with tumor progression.
- Measure growth factor and cytokine responses in children and young adults with ependymoma after treatment with a second course of irradiation, and explore associations between these and other measures of CNS effects and clinical and treatment factors. Descriptively compare findings for patients treated with an initial course of irradiation.
- To conduct a variety of exploratory molecular analyses on tumor samples (and blood where a germline control is required), including but not limited to broad (genome-wide / array-based) or focused (gene-specific) analyses at the DNA, RNA, or protein level and next generation (whole genome, exome, transcriptome) sequencing in an effort to improve the investigators understanding of ependymoma biology, and to explore associations between molecular findings and treatment response and various side effects including vasculopathy, hearing loss, cognitive deficits, and growth hormone deficiency and other measures as appropriate.
- To explore the association of chemotherapy given prior to re-irradiation with progression-free survival and overall survival distributions
- To compare the progression-free and overall survival distributions for children (age >3 years) and young adults with recurrent ependymoma and 1g gain treated with a second course of irradiation (focal or craniospinal) while monitoring for excessive central nervous system necrosis.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Toronto, Canada
- Princess Margaret Cancer Centre
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Tennessee
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Memphis, Tennessee, United States, 38105
- St. Jude Children's Research Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Progressive intracranial ependymoma after prior focal irradiation
- Patients aged 1-21 years at the time of enrollment
- Adequate performance status (ECOG < 3) and research participant does not require mechanical ventilation
- Interval from start of initial radiation therapy to enrollment > 9 months
Exclusion Criteria:
- Prior craniospinal irradiation
- Pregnant women are excluded from enrollment on this study because radiation therapy is an agent with the potential for teratogenic or abortifacient effects
- Any patient with both metastatic ependymoma and age < 3 years at the time of enrollment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Stratum 1: Local Failure
Participants exhibit an initial pattern of failure that is local (disease confined to primary site). Treatment is surgery and a second course of focal irradiation. The total dose for the second course of irradiation will be 54Gy. Participants may receive one or both: Photon therapy or proton therapy. Participants receive ^1^8F-fluorodeoxyglucose and ^1^1C-methionine to aid in tumor visualization. |
Radiation therapy on this protocol will be based on extent of disease, extent of resection and location.
The allowed treatment modalities include conformal or intensity-modulated radiation therapy using photons or proton therapy using double-scattering or spot-scanning methods.
The general goal is to initiate radiation therapy within 12 weeks of last surgery performed at the time of recurrence.
Other Names:
When applicable, surgery will be used to remove metastases.
The goal of surgery is to achieve gross total resection of all imaging visible residual tumor.
Other Names:
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
Participants will receive one or both: Photon or proton therapy.
Other Names:
Participants will receive one or both: Photon or proton therapy.
Other Names:
|
Experimental: Stratum 2: Metastatic Failure
Participants exhibit an initial pattern of failure that is metastatic (neuraxis metastatic disease without equivocal evidence of local failure). Treatment is surgery and craniospinal irradiation. Craniospinal irradiation (36-39.6Gy) will include focal boost treatment of metastatic sites (54-59.4Gy) depending on location, extent of resection and target volume. Participants may receive one or both: Photon therapy or proton therapy. Participants receive ^1^8F-fluorodeoxyglucose and ^1^1C-methionine to aid in tumor visualization. |
Radiation therapy on this protocol will be based on extent of disease, extent of resection and location.
The allowed treatment modalities include conformal or intensity-modulated radiation therapy using photons or proton therapy using double-scattering or spot-scanning methods.
The general goal is to initiate radiation therapy within 12 weeks of last surgery performed at the time of recurrence.
Other Names:
When applicable, surgery will be used to remove metastases.
The goal of surgery is to achieve gross total resection of all imaging visible residual tumor.
Other Names:
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
Participants will receive one or both: Photon or proton therapy.
Other Names:
Participants will receive one or both: Photon or proton therapy.
Other Names:
|
Experimental: Stratum 3: Local and Metastatic Failure
Participants exhibit an initial pattern of failure that is both local and metastatic (neuraxis metastatic disease with equivocal evidence of local failure). Treatment is surgery and craniospinal irradiation. Participants may receive one or both: Photon therapy or proton therapy. Participants receive ^1^8F-fluorodeoxyglucose and ^1^1C-methionine to aid in tumor visualization. |
Radiation therapy on this protocol will be based on extent of disease, extent of resection and location.
The allowed treatment modalities include conformal or intensity-modulated radiation therapy using photons or proton therapy using double-scattering or spot-scanning methods.
The general goal is to initiate radiation therapy within 12 weeks of last surgery performed at the time of recurrence.
Other Names:
When applicable, surgery will be used to remove metastases.
The goal of surgery is to achieve gross total resection of all imaging visible residual tumor.
Other Names:
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
Participants will receive one or both: Photon or proton therapy.
Other Names:
Participants will receive one or both: Photon or proton therapy.
Other Names:
|
Experimental: Stratum 4: Local Failure
Local Failure Participants exhibit an initial pattern of failure that is local (disease confined to primary site). Age is >36 months at time of enrollment to <21 years. Tumor shows presence of 1q gain. Treatment is optional craniospinal irradiation. Participants may receive one or both: Photon therapy or proton therapy. Participants receive ^1^8F-fluorodeoxyglucose and ^1^1C-methionine to aid in tumor visualization. |
Radiation therapy on this protocol will be based on extent of disease, extent of resection and location.
The allowed treatment modalities include conformal or intensity-modulated radiation therapy using photons or proton therapy using double-scattering or spot-scanning methods.
The general goal is to initiate radiation therapy within 12 weeks of last surgery performed at the time of recurrence.
Other Names:
When applicable, surgery will be used to remove metastases.
The goal of surgery is to achieve gross total resection of all imaging visible residual tumor.
Other Names:
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
Participants will receive one or both: Photon or proton therapy.
Other Names:
Participants will receive one or both: Photon or proton therapy.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
3-year progression-free survival rate
Time Frame: 2 years follow-up after initiation of radiation therapy for the last patient enrolled
|
2 years follow-up after initiation of radiation therapy for the last patient enrolled
|
3-year overall survival rate
Time Frame: 2 years follow-up after initiation of radiation therapy for the last patient enrolled
|
2 years follow-up after initiation of radiation therapy for the last patient enrolled
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence rate of neurological deficits
Time Frame: Through 5 years after initiation of second course of irradiation
|
Evaluation will be in children and young adults with ependymoma treated with a second course of irradiation. Outcomes will be reported by p-values. |
Through 5 years after initiation of second course of irradiation
|
Incidence rate of ophthalmological deficits
Time Frame: Through 5 years after initiation of second course of irradiation
|
Evaluation will be in children and young adults with ependymoma treated with a second course of irradiation. Outcome will be reported with p values. |
Through 5 years after initiation of second course of irradiation
|
Incidence rate of audiological deficits
Time Frame: Through 5 years after initiation of second course of irradiation
|
Evaluation will be in children and young adults with ependymoma treated with a second course of irradiation. Outcome will be reported with p-values. |
Through 5 years after initiation of second course of irradiation
|
Incidence rate of endocrine deficits
Time Frame: Through 5 years after initiation of second course of irradiation
|
Evaluation will be in children and young adults with ependymoma treated with a second course of irradiation. Outcome will be reported with p-values. |
Through 5 years after initiation of second course of irradiation
|
Number of neurocognitive deficits
Time Frame: Through 5 years after initiation of second course of irradiation
|
Through 5 years after initiation of second course of irradiation
|
|
Mean change in quality of life by treatment arm
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy.
|
Baseline through 5 years after initiation of radiation therapy
|
Mean change in measured task sets
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy. Measured task sets: BOT2 (4-21 years old) and PPT (≥22 years old).
The above scores will be standardized into z-scores/T-scores for data analysis based on normative data. |
Baseline through 5 years after initiation of radiation therapy
|
Mean change in physical function
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy. Self-reported instruments (PROMIS): Three questionnaires.
The above scores will be standardized into z-scores/T-scores for data analysis based on normative data |
Baseline through 5 years after initiation of radiation therapy
|
Mean change in body mass index (kg/m2)
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy
|
Baseline through 5 years after initiation of radiation therapy
|
Mean change in waist/hip ratio (cm/cm)
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy.
|
Baseline through 5 years after initiation of radiation therapy
|
Mean change in ankle dorsiflexion
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy. Ankle dorsiflexion active and passive range of motion: measured by goniometer, and recorded as an angle (degree). |
Baseline through 5 years after initiation of radiation therapy
|
Mean change in overall flexibility in cm
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy. Overall flexibility: measured by sit and reach test, and recorded as a length (cm). |
Baseline through 5 years after initiation of radiation therapy
|
Proportion change in balance
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy. Balance measured by Measured by sensory organization test (SOT), and the result from the test is the equilibrium score, a percentage range from 0% to 100%, with the higher percentage, the better balance. The outcome is a binary variable with a cutoff score of < 70% indicates future risk for a fall. |
Baseline through 5 years after initiation of radiation therapy
|
Mean change in fine motor coordination
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy. Fine motor coordination (finger and hand coordination). Measured by Composite Cerebellar Functional Severity Score (CCFS), and the outcome is an age-adjusted z-score and log transformed. |
Baseline through 5 years after initiation of radiation therapy
|
Mean change in overall coordination
Time Frame: Fine motor coordination (finger and hand coordination).
|
Baseline is defined as day 1 of radiation therapy. Overall coordination measured by brief ataxia rating scale (five-item questionnaire). The outcome is a total scale range from 0 to 22. |
Fine motor coordination (finger and hand coordination).
|
Mean change of lower extremity strength and power
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy. Lower extremity strength measured by BiodexIII. The outcomes are peak torque value/body weight ratios at different speeds of motion. The scores will be standardized into z-scores for data analysis based on normative data. |
Baseline through 5 years after initiation of radiation therapy
|
Mean change in hand grip strength
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy. Hand grip strength is measured by a Jamar hand held dynamometer and recorded in kilograms (kg). The scores will be standardized into z-scores for data analysis based on normative data. |
Baseline through 5 years after initiation of radiation therapy
|
Mean change in resting energy expenditure
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy. Resting energy expenditure is measured with indirect calorimetry after an overnight fast and recorded as REE (kcal/day). The scores will be standardized into z-scores for data analysis based on normative data. |
Baseline through 5 years after initiation of radiation therapy
|
Mean change in cardiopulmonary exercise test (CPET)
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as day 1 of radiation therapy. Cardiopulmonary exercise test (CPET) will be completed on a treadmill using the Balke protocol or cycle ergometer using an incremental ramping protocol. The outcome is recorded as VO2max (ml/kg/min). The scores will be standardized into z-scores for data analysis based on normative data. |
Baseline through 5 years after initiation of radiation therapy
|
Longitudinal change of size (or extent if leptomeningeal dissemination) of residual tumor
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as the last MRI prior to initiation of radiation therapy.
|
Baseline through 5 years after initiation of radiation therapy
|
Longitudinal change of incidence and severity of structural effects of normal brain
Time Frame: Baseline through 5 years after initiation of radiation therapy
|
Baseline is defined as the last MRI prior to initiation of radiation therapy.
|
Baseline through 5 years after initiation of radiation therapy
|
Longitudinal change in gray and white matter tissues
Time Frame: Baseline to recovery of gray and white matter tract injury, up to a maximum of 5 years
|
This outcome will be evaluated by neuroimaging.
Baseline is defined as day 1 of radiation therapy.
|
Baseline to recovery of gray and white matter tract injury, up to a maximum of 5 years
|
Longitudinal change of individual variation and risk factors in gray and white matter tissues
Time Frame: Baseline to recovery of gray and white matter tract injury, up to a maximum of 5 years
|
Baseline is defined as day 1 of radiation therapy.
|
Baseline to recovery of gray and white matter tract injury, up to a maximum of 5 years
|
Change over time in imaging metrics
Time Frame: Baseline to recovery of gray and white matter tract injury, up to a maximum of 5 years
|
Baseline is defined as day 1 of radiation therapy.
|
Baseline to recovery of gray and white matter tract injury, up to a maximum of 5 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Avidity of ependymoma to 18F-fluorodeoxyglucose and 11C-methionine PET prior to radiation therapy
Time Frame: Baseline
|
Baseline is the last FDG-PET and MET-PET prior to initiation of radiation therapy.
|
Baseline
|
Longitudinal change of avidity of ependymoma to 18F-fluorodeoxyglucose and 11C-methionine PET prior to radiation therapy
Time Frame: 12, 24 and 36 months after second course of irradiation
|
Correlation of avidity of ependymoma to 18F-fluorodeoxyglucose and 11C-methionine PET prior to radiation therapy with progression-free survival will be reported
|
12, 24 and 36 months after second course of irradiation
|
Longitudinal change of necrosis measured with MET/FDG and necrosis measured with MRI
Time Frame: Baseline, and at 12, 24 and 36 month
|
Association between necrosis measured with MET/FDG vs. MRI Baseline is defined as day 1 of radiation therapy (RT).
|
Baseline, and at 12, 24 and 36 month
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Mean change over time in cytokine levels
Time Frame: Baseline through 5 years after radiation therapy
|
Baseline is defined as day 1 of radiation therapy.
|
Baseline through 5 years after radiation therapy
|
Genetic variations in germline
Time Frame: Baseline
|
Evaluate will be of genetic variations in germline associated with treatment response and side effects. P-values will be reported. Baseline is defined as day 1 of radiation therapy. |
Baseline
|
3-year progression-free survival (PFS) rates by chemotherapy groups
Time Frame: 2 years after initiation of irradiation for the last patient enrolled
|
2 years after initiation of irradiation for the last patient enrolled
|
|
3 year overall survival (OS) rates by chemotherapy groups
Time Frame: 2 years after initiation of irradiation for the last patient enrolled
|
2 years after initiation of irradiation for the last patient enrolled
|
Collaborators and Investigators
Investigators
- Principal Investigator: Thomas E. Merchant, DO, PhD, St. Jude Children's Research Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- RERTEP
- NCI-2014-00906 (Registry Identifier: NCI Clinical Trial Registration Program)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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