Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Neurocognitive Impact and Dose-Effect Relationship of Hippocampal Avoidance During Whole Brain Radiotherapy Plus Simultaneous Integrated Boost - A Prospective Follow-up Study

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: NCT03223675
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : March 11, 2021
Sponsor:
Information provided by (Responsible Party):
Chang Gung Memorial Hospital

Tracking Information
First Submitted Date  ICMJE June 22, 2017
First Posted Date  ICMJE July 21, 2017
Last Update Posted Date March 11, 2021
Actual Study Start Date  ICMJE April 1, 2016
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2017)
  • The primary endpoint is delayed recall, as determined by the change/decline in verbal memory (WMS III- Word List score) from the baseline assessment to 4 months after the start of HS-WBRT. [ Time Frame: 4 months after the start of HS-WBRT ]
    Neurocognitive assessment: including memory, executive functions, and psychomotor speed. This neurocognitive outcome was delayed recall, as determined by the change/decline in verbal memory [Wechsler Memory Scale - 3rd edition (WMS III) - Word List score] from the baseline assessment to 4 months after the start of the course of WBRT with hippocampus sparing (HS-WBRT). Additionally, the follow-up of neurocognitive assessment will also be administered at 12 months and up to 18 months after the start of HS-WBRT
  • The primary endpoint is delayed recall, as determined by the change/decline in non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of HS-WBRT [ Time Frame: 4 months after the start of HS-WBRT ]
    Neurocognitive assessment: including memory, executive functions, and psychomotor speed. This neurocognitive outcome was delayed recall, as determined by the change/decline in non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of the course of WBRT with hippocampus sparing (HS-WBRT). Additionally, the follow-up of neurocognitive assessment will also be administered at 12 months and up to 18 months after the start of HS-WBRT.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2017)
  • Overall survival time, indicated by the time from the date of recruitment to the date of expiring [ Time Frame: up to 18 months ]
  • The time from the date of recruitment to that of intracranial progression/failure noted on brain MRI or CT [ Time Frame: up to 18 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neurocognitive Impact and Dose-Effect Relationship of Hippocampal Avoidance During Whole Brain Radiotherapy Plus Simultaneous Integrated Boost - A Prospective Follow-up Study
Official Title  ICMJE Not Provided
Brief Summary For newly-diagnosed patients with brain metastasis, whole brain radiation therapy (WBRT) probably remains a common palliative management even for those with oligometastatic brain disease. However, WBRT-related late sequelae, particularly a decline in neurocognitive functions (NCFs), are a major concern. More importantly, in patients with limited brain metastases and a fair/good performance status, sparing the radiosensitive and vulnerable structures which are responsible for essential NCFs during the WBRT course is one of the reasonable strategies to postpone and prevent the development of WBRT-induced neurocognitive impairments. Actually, radiation-related neurocognitive dysfunction is usually characterized as a decline involving learning and memory, in which the extremely radiosensitive hippocampus indeed plays a critical role. In addition to the neurocognitive preservation by virtue of sparing the radiosensitive structures like the hippocampus, durable intracranial tumor control critically depends on an escalated radiotherapeutic dose level which is adequate enough to eradicate gross metastatic brain lesions. Therefore, in order to achieve both hippocampal sparing and simultaneous integrated boost(s) to gross metastatic foci, a specialized WBRT technique, hippocampal avoidance during WBRT plus simultaneous integrated boost (SIB) will be adopted in this prospective study. Moreover, the dose-effect relationship would be analyzed in order to explore the correlation between the equivalent uniform dose (EUD) irradiating the hippocampus and the neurocognitive change/decline after the above WBRT course measured by objective neurocognitive test tools. Newly-diagnosed cancer patients harboring 1-3 gross metastatic lesions but still in fair/good performance statuses are potentially eligible. All recruited patients should receive baseline functional brain MRI examination and baseline neurobehavioral assessment. Treatment planning will be designed via the technique of volumetric-modulated arc therapy (VMAT) to achieve both hippocampal avoidance and simultaneous integrated boost(s) to gross metastatic lesions. Except for the above regions for which conformal avoidance or SIB is attempted, the prescribed dose to the remaining brain parenchyma will be consistently 3000 cGy in 12 fractions. Accordingly, a battery of neuropsychological measures, which includes 7 standardized neuropsychological tests (e.g., executive functions, verbal and non-verbal memory, working memory, and psychomotor speed), is used to evaluate neurobehavioral functions for our registered patients. The primary outcome measure is delayed recall, as determined by the change/decline in verbal memory or non-verbal memory, from the baseline assessment to 4 months after the start of the WBRT course. This prospective cohort study aims to examine thoroughly the impact of a specialized WBRT technique, integrating both simultaneous integrated boost(s) delivered to gross metastatic foci and conformal hippocampal avoidance, on the status of NCF change/decline in patients with oligometastatic brain disease. It is anticipated that intracranial local control will be more sustainable and durable resulting from the escalated focal dose of SIBs. Ultimately, we also expect the dose-effect relationship will be clearly demonstrated after investigating the correlation between the hippocampal dosimetry and the status of NCF change/decline after receiving HA-WBRT plus SIB.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Metastasis
  • Brain Metastases
Intervention  ICMJE Radiation: hippocampal-sparing WBRT
Study Arms  ICMJE Experimental: Hippocampus-sparing WBRT plus SIB
All studied patients should undergo a computed tomography (CT) simulation scan encompassing the entire head region with 1.25-mm slice thickness using a thermoplastic mask for immobilization. To achieve conformal hippocampal sparing during the delivery of whole brain radiation (WBRT) and simultaneous integrated boost(s) (SIB), the technique of volumetric modulated arc therapy (VMAT) via Linac-based RapidArc®.In terms of dose prescription, a dose of 30 Gy in 12 fractions was prescribed to whole-brain planning target volume (PTV) containing the normal brain parenchyma; an simultaneous integrated boost up to 120 - 150% is attempted to irradiate the gross metastatic foci.
Intervention: Radiation: hippocampal-sparing WBRT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 18, 2017)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with pathologically-confirmed non-hematopoietic malignancy who are referred for therapeutic or prophylactic WBRT
  • Good performance status no worse than Eastern Cooperative Group (ECOG) of 2 or a general status of Karnofsky Score (KPS) at least 70 %
  • The number and extent of brain metastatic lesions should be no more than three metastatic foci with a greatest diameter no more than 3 cm

Exclusion Criteria:

  • Patients with MRI-identified metastasis within 5 mm perihippocampally
  • Patients with metastasis involving the brain stem
  • Clinical suspicion of leptomeningeal spreading
  • Patients with a solitary brain metastatic lesion which had been totally removed
  • History of prior radiotherapy including stereotactic radiosurgery delivered to brain/head region for any reasons
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 84 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Chi-Cheng Chuang, M.D. +886-33281200 ext 2412 ccc2915@cgmh.org.tw
Contact: Shinn-Yn Lin, M.D. +886-33281200 ext 7172 rt3126@gmail.com
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03223675
Other Study ID Numbers  ICMJE 104-9176A3
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Chang Gung Memorial Hospital
Study Sponsor  ICMJE Chang Gung Memorial Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Chang Gung Memorial Hospital
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP