- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04801342
Neurocognitive Outcome of Bilateral or Unilateral Hippocampal Avoidance WBRT With Memantine for Brain Metastases
Neurocognitive Outcome of Conformal Whole Brain Radiotherapy With Bilateral or Unilateral Hippocampal Avoidance Plus Memantine for Brain Metastases: A Phase II Single Blind Randomized Trial
Brain metastases are the most common brain tumors in adults. It is estimated that around 10-30% of cancer patients would develop brain metastases during the course of their illness.
Whole brain radiotherapy (WBRT) is the treatment of choice for the majority of patients with brain metastases. WBRT yields high radiologic response rate (27~56%) and is effective in rapid palliation of neurologic symptoms as well as prolongs time to neurocognitive function decline caused by intracranial lesions. By using conventional fractionation, more than one- third of patients developed late neurocognitive toxicity while memory impairment was the most common symptom. The incidence is even higher when a formal and sensitive neurocognitive assessment was prospectively evaluated. With more long-term survivors nowadays, it has become increasingly important to minimize neurocognitive function decline and maintain quality of life in patients with brain metastasis.
The function of hippocampus is cooperation in learning, consolidation and retrieval of information and essential for formation of new memories. Bilateral and unilateral radiation injury of the hippocampus is known to alter learning and memory formation. Several preclinical studies support the hypothesis of hippocampus-mediated cognitive dysfunction by ionizing radiation. Clinical studies show increase in radiation dose to hippocampus is associated with subsequent neurocognitive function impairment in adult and pediatric patients. Furthermore, the result of phase III randomized trials suggested hippocampal avoidance plus Memantine significantly reduce the risk of neurocognitive impairment at 6 months from 68.2% in control arm with standard WBRT to 59.5% in experimental arm. In the investigator's prior investigation, patients received conformal WBRT with bilateral hippocampal avoidance also had significant less declines in verbal memory at 6 months.
Previous studies showed the right and left hippocampus exert different neurocognitive functions. Several retrospective studies also demonstrated that the radiation dose to the left hippocampus is more related to neurocognitive impairment. Planning study and investigation showed that by avoiding the left hippocampus alone, the radiation dose to the spared unilateral hippocampus is further decreased. In present study, a single blind randomized phase II trial is designed to investigate the effectiveness of neurocognitive function preservation using conformal WBRT with bilateral or unilateral hippocampal avoidance and memantine.
Study Overview
Status
Conditions
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Feng-Ming Hsu, MD, PhD
- Phone Number: 67061 +886-2-23123456
- Email: hsufengming@ntuh.gov.tw
Study Locations
-
-
-
Taipei, Taiwan, 100
- Recruiting
- National Taiwan University Hospital
-
Contact:
- Feng-Ming Hsu, MD
- Phone Number: 67061 +886-2-23123456
- Email: hsufengming@ntuh.gov.tw
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with a histologic diagnosis of non-hematopoietic malignancy and radiographic evidence of brain metastases
- Patients with brain metastasis outside a 5-mm margin around either hippocampus on gadolinium contrast enhanced MRI obtained within 30 days prior to registration
- Patients with brain metastasis who have not been or will not be treated with SRS, or have received SRS for ≤ 5 intracranial metastatic lesion(s)
- No evidence of diffuse leptomeningeal metastasis on gadolinium- enhanced MRI within 30 days prior registration
- Age ≥ 20 years
- Karnofsky Performance Status ≥ 60%
- Life expectancy of ≥ 6 months.
- Women of childbearing potential and male participants must practice adequate contraception
- Patients must be able to comply with the study protocol and follow-up schedules and provide study-specific informed consent
Exclusion Criteria:
- Prior radiotherapy to brain or radiosurgery to > 5 intracranial metastatic lesion(s) or the biological equivalent dose in 2-Gy fractions was greater than 7.3Gy to 40% of the volume of bilateral hippocampus from prior radiosurgery
- Serum creatinine > 2.0 mg/dL within 30 days prior registration
- Serum urea nitrogen > 20 mg/dL within 30 days prior registration
- Contraindication to MR imaging such as implanted metal devices or foreign bodies, severe claustrophobia
Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:
- Uncontrolled active infection requiring intravenous antibiotics at the time of registration
- Transmural myocardial infarction ≤ 6 months prior to registration
- Unstable angina or congestive heart failure requiring hospitalization ≤ 6 months prior to registration
- Life-threatening uncontrolled clinically significant cardiac arrhythmias
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- Uncontrolled psychiatric disorder
- Will receive any other investigational agent or chemotherapy during WBRT
- Current use of Memantine HCL or Allergy to Memantine HCL
- Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic
- Pregnant or breast-feeding women
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Unilateral Hippocampal Avoidance WBRT with Memantine
Conformal whole brain radiotherapy with unilateral hippocampal avoidance and Concurrent use of Memantine HCL
|
Conformal Whole Brain Radiotherapy 30 Gy in 10 fractions with Unilateral Hippocampal Avoidance using Intensity modulated radiotherapy, Volumetric arc therapy, or Tomotherapy
Other Names:
Start from day 1 of WBRT orally for 24 weeks and escalating doses over the first 4 weeks
Other Names:
|
Active Comparator: Bilateral Hippocampal Avoidance WBRT with Memantine
Conformal whole brain radiotherapy with bilateral hippocampal avoidance and Concurrent use of Memantine HCL
|
Start from day 1 of WBRT orally for 24 weeks and escalating doses over the first 4 weeks
Other Names:
Conformal Whole Brain Radiotherapy 30 Gy in 10 fractions with Bilateral Hippocampal Avoidance using Intensity modulated radiotherapy, Volumetric arc therapy, or Tomotherapy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hopkins Verbal Learning Test-Revised (HVLT-R) memory score
Time Frame: At 6 months after WBRT
|
Decline in Hopkins Verbal Learning Test-Revised (HVLT-R) memory score (sum of total recall and recognition index) from baseline to 6 months after the start of conformal whole brain radiotherapy (WBRT) with bilateral or unilateral hippocampal avoidance for multiple brain metastases.
HVLT-R Total recall raw scores ranged from 0 to 36, recognition index ranged from 0 to 12.
The higher the score indicated better short term memory preservation
|
At 6 months after WBRT
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Neurocognitive function by a standardized neurocognitive battery Hopkins Verbal Learning Test-Revised (HVLT-R)
Time Frame: at 1, 2, 4, 6, 9, 12 months after WBRT, and then every 3 months until date of death from any cause, assessed up to 24 months
|
Evaluate neurocognitive function by a standardized neurocognitive battery Hopkins Verbal Learning Test-Revised (HVLT-R) with Total recall score (range from 0 to 36), delayed recall score (range from 0 to 12) and recognition index (range from 0 to 12).
The higher the score indicated better short term memory preservation.
|
at 1, 2, 4, 6, 9, 12 months after WBRT, and then every 3 months until date of death from any cause, assessed up to 24 months
|
Neurocognitive function by a standardized neurocognitive battery Trail Making Test Part A & B
Time Frame: at 1, 2, 4, 6, 9, 12 months after WBRT, and then every 3 months until date of death from any cause, assessed up to 24 months
|
Evaluate neurocognitive function by a standardized neurocognitive battery Trail Making Test Part A & B. TMT-A and B tested the executive function documented with time needed for complete test with no upper limit of range.
The longer the time needed, the worse executive function patients preserved.
|
at 1, 2, 4, 6, 9, 12 months after WBRT, and then every 3 months until date of death from any cause, assessed up to 24 months
|
Neurocognitive function by a standardized neurocognitive battery Controlled Oral Word Association Test
Time Frame: at 1, 2, 4, 6, 9, 12 months after WBRT, and then every 3 months until date of death from any cause, assessed up to 24 months
|
Evaluate neurocognitive function by a standardized neurocognitive battery Controlled Oral Word Association Test.
Patients are given one phoneme at a time and instructed to say aloud as many words beginning with that phoneme as they could within 1 minute, for a total of three phonemes in 3 minutes.
The more the words patients able to say in limit time, the better outcome presented.
|
at 1, 2, 4, 6, 9, 12 months after WBRT, and then every 3 months until date of death from any cause, assessed up to 24 months
|
Patient reported outcome (Quality of Life questionnaire)
Time Frame: at 1, 2, 4, 6, 9, 12 months after WBRT, and then every 3 months until date of death from any cause, assessed up to 24 months
|
EORTC Quality of Life-Core 30 questionnaire module (at question 1 to 27, range from 1 to 4; at question 29 and 30, range from 1 to 7) Quality of Life questionnaire-Brain.
|
at 1, 2, 4, 6, 9, 12 months after WBRT, and then every 3 months until date of death from any cause, assessed up to 24 months
|
Patient reported outcome (Cognitive Functioning questionnaire)
Time Frame: at 1, 2, 4, 6, 9, 12 months after WBRT, and then every 3 months until date of death from any cause, assessed up to 24 months
|
Function Assessment Cancer Therapy for patients with Cognitive function issue
|
at 1, 2, 4, 6, 9, 12 months after WBRT, and then every 3 months until date of death from any cause, assessed up to 24 months
|
Acute toxicity (Common Toxicity Criteria for Adverse Events version 4)
Time Frame: From date of WBRT until 90 days after radiotherapy starts
|
Common Toxicity Criteria for Adverse Events version 4
|
From date of WBRT until 90 days after radiotherapy starts
|
Late toxicity (Common Toxicity Criteria for Adverse Events version 4)
Time Frame: From 90 days after WBRT starts until the date of death from any cause, up to 60 months
|
Common Toxicity Criteria for Adverse Events version 4
|
From 90 days after WBRT starts until the date of death from any cause, up to 60 months
|
Intracranial progression (Number of participant with intracranial progression on MRI of brain)
Time Frame: From date of enrolment until the date of first documented intracranial progression or date of death from any cause, whichever came first, assessed up to 60 months
|
Number of participant with intracranial progression on MRI of brain
|
From date of enrolment until the date of first documented intracranial progression or date of death from any cause, whichever came first, assessed up to 60 months
|
Overall survival
Time Frame: From date of enrollment until the date of death from any cause, assessed up to 60 months
|
Number of patients died
|
From date of enrollment until the date of death from any cause, assessed up to 60 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Genomic risk of neurocognitive decline after WBRT
Time Frame: At 4 months after radiotherapy
|
Number of participants with Genomic risk of neurocognitive impairment after WBRT
|
At 4 months after radiotherapy
|
Collaborators and Investigators
Investigators
- Principal Investigator: Feng-Ming Hsu, MD, PhD, National Taiwan University Hospital
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
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
- Pathologic Processes
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms by Site
- Neoplastic Processes
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Neoplasms
- Neoplasm Metastasis
- Brain Neoplasms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Dopamine Agents
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Memantine
Other Study ID Numbers
- 201901084MINA
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
Clinical Trials on Metastatic Malignant Neoplasm to Brain
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedMalignant Neoplasm | Metastatic Malignant Neoplasm to the BoneUnited States
-
Chuangzhen ChenRecruitingRadiotherapy | Immune Checkpoint Blockade | Metastatic Extracranial Malignant Solid Neoplasm | Resistance to ImmunotherapyChina
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingMetastatic Malignant Solid Neoplasm | Metastatic Malignant Neoplasm in the BrainUnited States
-
Sameek RoychowdhuryNational Cancer Institute (NCI)WithdrawnLocally Advanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | ALK Gene Mutation | Metastatic Malignant Neoplasm in the Brain | Advanced Malignant Neoplasm | ALK Fusion Protein Expression | Metastatic Malignant Neoplasm in the Central Nervous System | ROS1 Gene Mutation | ALK Gene... and other conditionsUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingMalignant Solid Neoplasm | Metastatic Malignant Neoplasm in the BrainUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedMalignant Neoplasm | Metastatic Malignant Neoplasm in the BrainUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingAdvanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | Metastatic Malignant Neoplasm in the Liver | Metastatic Malignant Neoplasm in the LungUnited States
-
M.D. Anderson Cancer CenterTerminatedLeukemia | Metastatic Malignant Neoplasm to the Leptomeninges | Lymphoid MalignanciesUnited States
-
National Cancer Institute (NCI)Active, not recruitingAdvanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | Metastatic Malignant Neoplasm in the Liver | Unresectable Solid NeoplasmUnited States, Canada
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedMetastatic Malignant Neoplasm | Unresectable Malignant Neoplasm | Advanced Malignant NeoplasmUnited States
Clinical Trials on Conformal Whole Brain Radiotherapy with Unilateral Hippocampal Avoidance
-
Kaohsiung Medical University Chung-Ho Memorial...UnknownBrain Metastases | Neurocognitive FunctionTaiwan
-
University College, LondonCancer Research UK; The Brain Tumour CharityCompletedBrain MetastasesUnited Kingdom
-
University Hospital, EssenUnknown
-
NRG OncologyNational Cancer Institute (NCI)CompletedCognitive Impairment | Metastatic Malignant Neoplasm in the Brain | Solid NeoplasmUnited States, Canada
-
University Hospital, GhentTerminated
-
Medical University InnsbruckRecruiting
-
Sheba Medical CenterUnknown
-
Mundipharma Research LimitedCompletedBrain Metastases | Solid Tumour Neoplastic MeningitisAustria, Germany