A Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma

Titre officiel

A Phase II Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma

Sommaire:

L’objectif principal de cette étude est de déterminer si une intervention chirurgicale et une seconde radiothérapie aideront à traiter l’épendymome qui est revenu après le traitement initial. Les doses combinées des deux premières séries de radiothérapie sont plus élevées que la norme habituelle de soins. Les chercheurs étudieront les effets et les effets secondaires d’une intervention chirurgicale et d’une seconde radiothérapie. Ils évalueront et étudieront également les tissus tumoraux et le sang afin d’en apprendre davantage sur la tumeur et la façon dont celle-ci répond ou non aux traitements et utiliseront l’imagerie par résonance magnétique (IRM) et la tomographie par émission de positrons (TEP) pour déterminer si ces modalités peuvent permettre de prévoir la réponse tumorale et la récidive tumorale. Les participants feront l’objet d’un suivi jusqu’à cinq ans après leur inscription. Les évaluations au cours de la radiothérapie seront effectuées toutes les semaines pendant une période maximale de sept semaines. D’autres évaluations seront effectuées à l’inscription, tous les quatre mois à partir de l’inscription jusqu’à trois ans, et tous les six mois pendant la 4e et la 5e année.

Description de l'essai

Primary Outcome:

  • 3-year progression-free survival rate
  • 3-year overall survival rate
Secondary Outcome:
  • Incidence rate of neurological deficits
  • Incidence rate of ophthalmological deficits
  • Incidence rate of audiological deficits
  • Incidence rate of endocrine deficits
  • Number of neurocognitive deficits
  • Mean change in quality of life by treatment arm
  • Mean change in measured task sets
  • Mean change in physical function
  • Mean change in body mass index (kg/m2)
  • Mean change in waist/hip ratio (cm/cm)
  • Mean change in ankle dorsiflexion
  • Mean change in overall flexibility in cm
  • Proportion change in balance
  • Mean change in fine motor coordination
  • Mean change in overall coordination
  • Mean change of lower extremity strength and power
  • Mean change in hand grip strength
  • Mean change in resting energy expenditure
  • Mean change in cardiopulmonary exercise test (CPET)
  • Longitudinal change of size (or extent if leptomeningeal dissemination) of residual tumour
  • Longitudinal change of incidence and severity of structural effects of normal brain
  • Longitudinal change in gray and white matter tissues
  • Longitudinal change of individual variation and risk factors in gray and white matter tissues
  • Change over time in imaging metrics
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; tumour 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 tumour 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 tumour 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 tumour 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.

Voir cet essai sur ClinicalTrials.gov

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