Clinical trial NCT02125786: A Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
Official title: A Phase II Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Ependymoma
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2014-04-29
Enrollment: 68
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 3-year Progression-free Survival Rate
timeFrame: 2 years follow-up after initiation of radiation therapy for the last patient enrolled
measure: 3-year Overall Survival Rate
timeFrame: 2 years follow-up after initiation of radiation therapy for the last patient enrolled
Secondary outcomes:
measure: Incidence Rate of Neurological Deficits
timeFrame: Through 5 years after initiation of second course of irradiation
measure: Incidence Rate of Ophthalmological Deficits
timeFrame: Through 5 years after initiation of second course of irradiation
measure: Incidence Rate of Audiological Deficits
timeFrame: Through 5 years after initiation of second course of irradiation
measure: Incidence Rate of Endocrine Deficits
timeFrame: Through 5 years after initiation of second course of irradiation
measure: Number of Neurocognitive Deficits
timeFrame: Through 5 years after initiation of second course of irradiation
measure: Mean Change in Quality of Life by Treatment Arm
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Mean Change in Measured Task Sets
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Mean Change in Physical Function
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Mean Change in Body Mass Index (kg/m2)
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Mean Change in Waist/Hip Ratio (cm/cm)
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Mean Change in Ankle Dorsiflexion
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Mean Change in Overall Flexibility in cm
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Proportion Change in Balance
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Mean Change in Fine Motor Coordination
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Mean Change in Overall Coordination
timeFrame: Fine motor coordination (finger and hand coordination).
measure: Mean Change of Lower Extremity Strength and Power
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Mean Change in Hand Grip Strength
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Mean Change in Resting Energy Expenditure
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Mean Change in Cardiopulmonary Exercise Test (CPET)
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Longitudinal Change of Size (or Extent if Leptomeningeal Dissemination) of Residual Tumor
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Longitudinal Change of Incidence and Severity of Structural Effects of Normal Brain
timeFrame: Baseline through 5 years after initiation of radiation therapy
measure: Longitudinal Change in Gray and White Matter Tissues
timeFrame: Baseline to recovery of gray and white matter tract injury, up to a maximum of 5 years
measure: Longitudinal Change of Individual Variation and Risk Factors in Gray and White Matter Tissues
timeFrame: Baseline to recovery of gray and white matter tract injury, up to a maximum of 5 years
measure: Change Over Time in Imaging Metrics
timeFrame: Baseline to recovery of gray and white matter tract injury, up to a maximum of 5 years
Other outcomes:
measure: Avidity of Ependymoma to 18F-fluorodeoxyglucose and 11C-methionine PET Prior to Radiation Therapy
timeFrame: Baseline
measure: Longitudinal Change of Avidity of Ependymoma to 18F-fluorodeoxyglucose and 11C-methionine PET Prior to Radiation Therapy
timeFrame: 12, 24 and 36 months after second course of irradiation
measure: Longitudinal Change of Necrosis Measured With MET/FDG and Necrosis Measured With MRI
timeFrame: Baseline, and at 12, 24 and 36 month
measure: Mean Change Over Time in Cytokine Levels
timeFrame: Baseline through 5 years after radiation therapy
measure: Genetic Variations in Germline
timeFrame: Baseline
measure: 3-year Progression-free Survival (PFS) Rates by Chemotherapy Groups
timeFrame: 2 years after initiation of irradiation for the last patient enrolled
measure: 3 Year Overall Survival (OS) Rates by Chemotherapy Groups
timeFrame: 2 years after initiation of irradiation for the last patient enrolled
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Thomas E. Merchant, DO, PhD
role: PRINCIPAL_INVESTIGATOR
References: