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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02125786
Recruitment Status : Recruiting
First Posted : April 29, 2014
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

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.


Condition or disease Intervention/treatment Phase
Ependymoma Radiation: Irradiation Procedure: Surgery Drug: ^1^8F-Fluorodeoxyglucose Drug: ^1^1C-methionine Device: Photon therapy Device: Proton therapy Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 99 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
Actual Study Start Date : May 7, 2014
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2028

Resource links provided by the National Library of Medicine


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: Irradiation
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:
  • Focal irradiation
  • Craniospinal irradiation

Procedure: Surgery
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 Name: Metastasectomy

Drug: ^1^8F-Fluorodeoxyglucose
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
  • 18F-FDG
  • Contrast Media

Drug: ^1^1C-methionine
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Name: Contrast Media

Device: Photon therapy
Participants will receive one or both: Photon or proton therapy.
Other Name: Photon linear accelerator

Device: Proton therapy
Participants will receive one or both: Photon or proton therapy.
Other Name: Proton synchroton

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: Irradiation
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:
  • Focal irradiation
  • Craniospinal irradiation

Procedure: Surgery
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 Name: Metastasectomy

Drug: ^1^8F-Fluorodeoxyglucose
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
  • 18F-FDG
  • Contrast Media

Drug: ^1^1C-methionine
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Name: Contrast Media

Device: Photon therapy
Participants will receive one or both: Photon or proton therapy.
Other Name: Photon linear accelerator

Device: Proton therapy
Participants will receive one or both: Photon or proton therapy.
Other Name: Proton synchroton

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: Irradiation
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:
  • Focal irradiation
  • Craniospinal irradiation

Procedure: Surgery
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 Name: Metastasectomy

Drug: ^1^8F-Fluorodeoxyglucose
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
  • 18F-FDG
  • Contrast Media

Drug: ^1^1C-methionine
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Name: Contrast Media

Device: Photon therapy
Participants will receive one or both: Photon or proton therapy.
Other Name: Photon linear accelerator

Device: Proton therapy
Participants will receive one or both: Photon or proton therapy.
Other Name: Proton synchroton

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: Irradiation
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:
  • Focal irradiation
  • Craniospinal irradiation

Procedure: Surgery
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 Name: Metastasectomy

Drug: ^1^8F-Fluorodeoxyglucose
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Names:
  • 18F-FDG
  • Contrast Media

Drug: ^1^1C-methionine
This is a contrast media that will be given intravenously to aid in tumor visualization.
Other Name: Contrast Media

Device: Photon therapy
Participants will receive one or both: Photon or proton therapy.
Other Name: Photon linear accelerator

Device: Proton therapy
Participants will receive one or both: Photon or proton therapy.
Other Name: Proton synchroton




Primary Outcome Measures :
  1. 3-year progression-free survival rate [ Time Frame: 2 years follow-up after initiation of radiation therapy for the last patient enrolled ]
  2. 3-year overall survival rate [ Time Frame: 2 years follow-up after initiation of radiation therapy for the last patient enrolled ]

Secondary Outcome Measures :
  1. 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.


  2. 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.


  3. 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.


  4. 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.


  5. Number of neurocognitive deficits [ Time Frame: Through 5 years after initiation of second course of irradiation ]
  6. 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.

  7. 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).

    • BOT2 outcome: total motor composite, a standardized score range from 20 to 80, with a mean of 50 and a standard deviation of 10.
    • PPT (7-item questionnaire) outcome: a score range from 0 to 28. The normative data is available from the human performance lab.

    The above scores will be standardized into z-scores/T-scores for data analysis based on normative data.


  8. 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.

    • Pediatric Physical Function - Mobility - SF1: 8-item questionnaire with the score range from 0 to 32.
    • Pediatric Physical Function - Upper Extremity - SF1: same as above.
    • Physical Function - SF1: 10-item questionnaire with the score range from 0 to 50.

    The above scores will be standardized into z-scores/T-scores for data analysis based on normative data


  9. 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

  10. 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.

  11. 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).


  12. 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).


  13. 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.


  14. 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.


  15. 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.


  16. 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.


  17. 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.


  18. 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.


  19. 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.


  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.


Other Outcome Measures:
  1. 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.

  2. 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

  3. 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).

  4. 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.

  5. 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.


  6. 3-year progression-free survival (PFS) rates by chemotherapy groups [ Time Frame: 2 years after initiation of irradiation for the last patient enrolled ]
  7. 3 year overall survival (OS) rates by chemotherapy groups [ Time Frame: 2 years after initiation of irradiation for the last patient enrolled ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02125786


Contacts
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Contact: Thomas E. Merchant, DO, PhD 866-278-5833 referralinfo@stjude.org

Locations
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United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Thomas E. Merchant, DO, PhD    866-278-5833    referralinfo@stjude.org   
Principal Investigator: Thomas E. Merchant, DO, PhD         
Canada
Princess Margaret Cancer Centre Recruiting
Toronto, Canada
Contact: Derek Tsang, MD    416-946-2121      
Principal Investigator: Derek Tsang, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Layout table for investigator information
Principal Investigator: Thomas E. Merchant, DO, PhD St. Jude Children's Research Hospital

Additional Information:
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Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT02125786    
Other Study ID Numbers: RERTEP
NCI-2014-00906 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Posted: April 29, 2014    Key Record Dates
Last Update Posted: August 20, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ependymoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Fluorodeoxyglucose F18
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action