A Randomized Phase 2 Trial of Memory Avoidance Whole Brain Radiotherapy Versus Hippocampal Avoidance Whole Brain Radiotherapy (Athena 2 Trial)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Hopkins Verbal Learning Test-Revised (HVLT-R)
研究概览
简要总结
Participants in this research study have cancer that has spread to their brain, called brain metastases. One treatment for this type of cancer is called whole brain radiotherapy that stays away from a specific neurocognitive substructure, called the hippocampus, combined with medication to preserve cognitive function. This study compares that approach to another approach of whole brain radiotherapy that stays away from additional structures that are thought to have a role in cognitive function. Researchers want to see if there is a difference in the preservation of cognitive function between these two approaches.
详细描述
Brain metastases happen when cancer spreads from its original location to the brain. For people with brain metastases, whole brain radiotherapy (WBRT) is important in reducing neurologic symptoms and maximizing intracranial control. Previous studies have shown that adding a drug called memantine to WBRT can help lower the risk of cognitive decline. Previous studies have also shown that hippocampal avoidance WBRT (HA-WBRT) with memantine can reduce the risk of cognitive decline even more. This combination is considered a standard of care option for people with brain metastases.
Even though HA-WBRT successfully reduces the risk of cognitive decline for people with brain metastases, many people still experience some cognitive decline. This means that new treatments are needed to better protect brain function for this population. While avoiding the hippocampus is helpful, there are still many other parts of the brain that may be affected by radiation. Important cognitive structures such as the amygdala, corpus callosum, and fornix are involved with memory processing, executive function, complex task performance, memory formation, and recall. Avoiding these cognitive structures can further preserve cognition for people receiving WBRT.
This study investigates the avoidance of additional cognitive structures (the amygdala, corpus callosum, fornix, hypothalamus, and pituitary) with memory avoidance whole brain radiotherapy (MA-WBRT). The safety and feasibility of MA-WBRT has already been demonstrated. The purpose of this study is to compare MA-WBRT with memantine to HA-WBRT with memantine, which is currently the standard of care for people with extensive brain metastases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have histologically, cytologically, or radiographically confirmed diagnosis of solid tumor with brain metastases
- •Age >18 years
- •Performance status: Karnofsky Performance Status (KPS) ≥ 70
- •Estimated life expectancy of at least 3 months
- •Participant must be considered a candidate for WBRT by the treating physician
- •Participant must be a primary English speaker and have the ability to understand and the willingness to sign an English written informed consent document
- •Participant has at least 10 brain metastases or is otherwise suitable for WBRT
排除标准
- •Prior whole brain radiation
- •Participant has Multiple Sclerosis, Alzheimer's, dementia, or mental disability
- •Pregnant or breastfeeding women are excluded from this study.
- •Participant is not able to receive an MRI
- •Participant has metastasis within avoidance neurocognitive substructures (hippocampus, amygdala, fornix, corpus callosum, pituitary, amygdala)
研究组 & 干预措施
Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT)
干预措施: Memantine (Drug)
Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT)
干预措施: MA-WBRT (Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT)) (Radiation)
Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT)
干预措施: HA-WBRT (Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT)) (Radiation)
Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT)
干预措施: Memantine (Drug)
结局指标
主要结局
Hopkins Verbal Learning Test-Revised (HVLT-R)
时间窗: Day 1 (prior to WBRT treatment)
The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.
Hopkins Verbal Learning Test-Revised (HVLT-R)
时间窗: Month 3
The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.
Hopkins Verbal Learning Test-Revised (HVLT-R)
时间窗: Month 6
The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.
Hopkins Verbal Learning Test-Revised (HVLT-R)
时间窗: Month 9
The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.
Controlled Oral Word Association Test (COWAT)
时间窗: Day 1 (prior to WBRT treatment)
The COWAT is a verbal fluency test that involves the examiner asking the participant to name as many words as they can that start with a designated letter, excluding proper nouns, for one minute. This is repeated three times. The examiner records the words provided by the participant, and the COWAT is scored by calculating the total number of acceptable words that the participant produced. Greater scores indicate a higher performance (greater cognitive capabilities) on the test.
Controlled Oral Word Association Test (COWAT)
时间窗: Month 3
The COWAT is a verbal fluency test that involves the examiner asking the participant to name as many words as they can that start with a designated letter, excluding proper nouns, for one minute. This is repeated three times. The examiner records the words provided by the participant, and the COWAT is scored by calculating the total number of acceptable words that the participant produced. Greater scores indicate a higher performance (greater cognitive capabilities) on the test.
Controlled Oral Word Association Test (COWAT)
时间窗: Month 6
The COWAT is a verbal fluency test that involves the examiner asking the participant to name as many words as they can that start with a designated letter, excluding proper nouns, for one minute. This is repeated three times. The examiner records the words provided by the participant, and the COWAT is scored by calculating the total number of acceptable words that the participant produced. Greater scores indicate a higher performance (greater cognitive capabilities) on the test.
Controlled Oral Word Association Test (COWAT)
时间窗: Month 9
The COWAT is a verbal fluency test that involves the examiner asking the participant to name as many words as they can that start with a designated letter, excluding proper nouns, for one minute. This is repeated three times. The examiner records the words provided by the participant, and the COWAT is scored by calculating the total number of acceptable words that the participant produced. Greater scores indicate a higher performance (greater cognitive capabilities) on the test.
Brief Visuospatial Memory Test-Revised (BVMT-R)
时间窗: Day 1 (prior to WBRT treatment)
The BVMT-R test involves a participant viewing a page of six figures for 10 seconds and then being asked to draw as many figures as they can remember in their correct places. This is repeated three times. Then, after a 25 minute interval, the examiner asks the participant to recall and draw the figures again. The BVMT-R is scored by summing how many items the participant correctly recalled for each trial. Higher scores indicate higher performance (greater cognitive capabilities) on the test.
Brief Visuospatial Memory Test-Revised (BVMT-R)
时间窗: Month 3
The BVMT-R test involves a participant viewing a page of six figures for 10 seconds and then being asked to draw as many figures as they can remember in their correct places. This is repeated three times. Then, after a 25 minute interval, the examiner asks the participant to recall and draw the figures again. The BVMT-R is scored by summing how many items the participant correctly recalled for each trial. Higher scores indicate higher performance (greater cognitive capabilities) on the test.
Brief Visuospatial Memory Test-Revised (BVMT-R)
时间窗: Month 6
The BVMT-R test involves a participant viewing a page of six figures for 10 seconds and then being asked to draw as many figures as they can remember in their correct places. This is repeated three times. Then, after a 25 minute interval, the examiner asks the participant to recall and draw the figures again. The BVMT-R is scored by summing how many items the participant correctly recalled for each trial. Higher scores indicate higher performance (greater cognitive capabilities) on the test.
Brief Visuospatial Memory Test-Revised (BVMT-R)
时间窗: Month 9
The BVMT-R test involves a participant viewing a page of six figures for 10 seconds and then being asked to draw as many figures as they can remember in their correct places. This is repeated three times. Then, after a 25 minute interval, the examiner asks the participant to recall and draw the figures again. The BVMT-R is scored by summing how many items the participant correctly recalled for each trial. Higher scores indicate higher performance (greater cognitive capabilities) on the test.
Trail Making Test (TMT)
时间窗: Day 1 (prior to WBRT treatment)
The TMT consists of two parts: Part A and Part B. In Part A, participants are asked to connect 25 circles numbered 1-25 in ascending order. In Part B, participants are asked to connect 13 circles alternating between numbers and letters in ascending order. Participants are asked to complete these tasks as quickly as they can without lifting their pen from the paper. The TMT is measured by the time in seconds that it takes participant to complete the tasks. Higher times indicate greater cognitive impairment.
Trail Making Test (TMT)
时间窗: Month 3
The TMT consists of two parts: Part A and Part B. In Part A, participants are asked to connect 25 circles numbered 1-25 in ascending order. In Part B, participants are asked to connect 13 circles alternating between numbers and letters in ascending order. Participants are asked to complete these tasks as quickly as they can without lifting their pen from the paper. The TMT is measured by the time in seconds that it takes participant to complete the tasks. Higher times indicate greater cognitive impairment.
Trail Making Test (TMT)
时间窗: Month 6
The TMT consists of two parts: Part A and Part B. In Part A, participants are asked to connect 25 circles numbered 1-25 in ascending order. In Part B, participants are asked to connect 13 circles alternating between numbers and letters in ascending order. Participants are asked to complete these tasks as quickly as they can without lifting their pen from the paper. The TMT is measured by the time in seconds that it takes participant to complete the tasks. Higher times indicate greater cognitive impairment.
Trail Making Test (TMT)
时间窗: Month 9
The TMT consists of two parts: Part A and Part B. In Part A, participants are asked to connect 25 circles numbered 1-25 in ascending order. In Part B, participants are asked to connect 13 circles alternating between numbers and letters in ascending order. Participants are asked to complete these tasks as quickly as they can without lifting their pen from the paper. The TMT is measured by the time in seconds that it takes participant to complete the tasks. Higher times indicate greater cognitive impairment.
Time to neurocognitive failure (NCF)
时间窗: Up to 12 months
Time to NCF is defined as cognitive decline on the reliable change index (RCI) on at least one of the following tests: HVLT-R, TMT A/B, COWAT, BVMT-R. Tests are defined below.
Hopkins Verbal Learning Test-Revised (HVLT-R)
时间窗: Month 12
The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.
Controlled Oral Word Association Test (COWAT)
时间窗: Month 12
The COWAT is a verbal fluency test that involves the examiner asking the participant to name as many words as they can that start with a designated letter, excluding proper nouns, for one minute. This is repeated three times. The examiner records the words provided by the participant, and the COWAT is scored by calculating the total number of acceptable words that the participant produced. Greater scores indicate a higher performance (greater cognitive capabilities) on the test.
Brief Visuospatial Memory Test-Revised (BVMT-R)
时间窗: Month 12
The BVMT-R test involves a participant viewing a page of six figures for 10 seconds and then being asked to draw as many figures as they can remember in their correct places. This is repeated three times. Then, after a 25 minute interval, the examiner asks the participant to recall and draw the figures again. The BVMT-R is scored by summing how many items the participant correctly recalled for each trial. Higher scores indicate higher performance (greater cognitive capabilities) on the test.
Trail Making Test (TMT)
时间窗: Month 12
The TMT consists of two parts: Part A and Part B. In Part A, participants are asked to connect 25 circles numbered 1-25 in ascending order. In Part B, participants are asked to connect 13 circles alternating between numbers and letters in ascending order. Participants are asked to complete these tasks as quickly as they can without lifting their pen from the paper. The TMT is measured by the time in seconds that it takes participant to complete the tasks. Higher times indicate greater cognitive impairment.
次要结局
未报告次要终点