Trial Outcomes & Findings for Avoiding the Hippocampus During Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases (NCT NCT01227954)

Last Updated: 2017-09-27

Results Overview

Change in Hopkins Verbal Learning Test-Revised delayed recall (HVLT\_R DR) score from baseline to 4 months after the start of treatment calculated as (baseline score - 4 month score)/ baseline score. A positive change indicates a decline in function. The HVLT-R assesses verbal learning and memory. It incorporates 6 different forms, helping to mitigate practice effects of repeated administrations. Each form includes 12 nouns (targets) with 4 words drawn from 3 semantic categories, which differ across the 6 forms. Delayed recall involves recalling a list of 12 targets after a 20-minute delay. The score is the sum of the number of targets correctly recalled. Percent change calculated as 100\*\[(baseline score - 4 month score)/ baseline score\]

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

113 participants

Primary outcome timeframe

Baseline and 4 months from start of treatment

Results posted on

2017-09-27

Participant Flow

Participant milestones

Participant milestones
Measure	WBRT With Hippocampal Avoidance Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Overall Study STARTED	113
Overall Study COMPLETED	100
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	WBRT With Hippocampal Avoidance Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Overall Study Protocol Violation	6
Overall Study No protocol treatment	7

Baseline Characteristics

Avoiding the Hippocampus During Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	WBRT With Hippocampal Avoidance n=100 Participants Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Age, Continuous	61 years n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 4 months from start of treatment

Population: Eligible patients who started treatment and had baseline and 4 month data

Outcome measures

Outcome measures
Measure	WBRT With Hippocampal Avoidance n=42 Participants Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Percent Change in Delayed Recall at 4 Months as Measured by the Hopkins Verbal Learning Test-Revised (HVLT-R)	7.0 percent change Interval -4.7 to 18.7

SECONDARY outcome

Timeframe: Baseline and 4 months from start of treatment

Population: Eligible patients who started treatment and had baseline and 4 month data

The score is the total number of correct responses made in remembering the list on three consecutive trials in a single session. A higher score indicates a better performance. Each patient served as her or his own control, and the percent change in ISLT score from baseline to 4 months was calculated as 100\*\[(baseline score - 4 month score)/ baseline score\].

Outcome measures

Outcome measures
Measure	WBRT With Hippocampal Avoidance n=34 Participants Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Percent Change at 4 Months in Auditory Learning Measured by Cogstate's International Shopping List Test (ISLT)	18.0 percent change Interval 5.5 to 30.5

SECONDARY outcome

Timeframe: Baseline and 4 months from start of treatment

Population: Eligible patients who started treatment and had baseline and 4 month data

The score is the arcsine of the square root of the proportion of correct responses. A higher score indicates a better performance. Each patient served as her or his own control, and the percent change in OCLT score from baseline to 4 months was calculated as 100\*\[(baseline score - 4 month score)/ baseline score\].

Outcome measures

Outcome measures
Measure	WBRT With Hippocampal Avoidance n=34 Participants Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Percent Change at 4 Months in Visual Learning Measured by Cogstate's One Card Learning Test (OCLT)	-8 percent change Interval -16.9 to 0.9

SECONDARY outcome

Timeframe: Baseline and 4 months from start of treatment

Population: Eligible patients who started treatment and completed at least one FACT-Br assessment

The FACT-Br is a 19-item self-report instrument designed to measure multidimensional quality of life in patients with brain cancer. It is to be administered with the FACT-General. The FACT-G is a validated, 27-item measure where a higher score represents higher QOL. In addition to a total QOL score, subscale scores for physical, functional, social and emotional well-being are produced. There are 5 responses options, 0=Not a lot to 4=Very much. All subscale items are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Scores range 0-108 for FACT-G total, 0-28 for physical, social, functional subscales, 0-24 for emotional subscale, 0-76 for brain subscale. Certain items must be reversed before it is added by subtracting the response from 4. Subscale requires \>= 50% of items to be completed while the overall response rate must be \> 80%. If items are missing, the subscale scores can be prorated.

Outcome measures

Outcome measures
Measure	WBRT With Hippocampal Avoidance n=80 Participants Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) Baseline	121.25 units on a scale Interval 74.0 to 158.0
Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) 2 month	111.94 units on a scale Interval 85.0 to 158.0
Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) 4 month	115 units on a scale Interval 81.0 to 159.0
Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) 6 month	126.22 units on a scale Interval 90.83 to 159.0

SECONDARY outcome

Timeframe: Baseline and 4 months from start of treatment

Population: Eligible patients who started treatment and completed at least one ADL assessment

The Barthel Index of Activities of Daily Living (ADL) is a 10-item assessment. Patient scores on the ADL range from 0 to 20 with lower scores indicating declining functional status.

Outcome measures

Outcome measures
Measure	WBRT With Hippocampal Avoidance n=81 Participants Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Quality of Life as Measured by the Barthel Index of Activities of Daily Living (ADL) Baseline	20 units on a scale Interval 10.0 to 21.0
Quality of Life as Measured by the Barthel Index of Activities of Daily Living (ADL) 2 month	20 units on a scale Interval 5.0 to 20.0
Quality of Life as Measured by the Barthel Index of Activities of Daily Living (ADL) 4 month	20 units on a scale Interval 7.0 to 20.0
Quality of Life as Measured by the Barthel Index of Activities of Daily Living (ADL) 6 month	20 units on a scale Interval 13.0 to 20.0

SECONDARY outcome

Timeframe: Analysis occurs after all patients have been on study for at least 4 months. (Patients are followed from registration to death or study termination whichever occurs first.)

Population: Eligible patients who started study treatment

Overall survival was measured from registration to the date of death or last known follow-up (censored). Kaplan-Meier estimator was used to median survival time and 95% confidence interval.

Outcome measures

Outcome measures
Measure	WBRT With Hippocampal Avoidance n=96 Participants Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Overall Survival	6.8 months Interval 4.8 to 10.9

SECONDARY outcome

Timeframe: Analysis occurs after all patients have been on study for at least 4 months. (Patients are followed from registration to death or study termination whichever occurs first.)

Population: Eligible patients who started study treatment

Progression (radiographic) is defined as an increase in perpendicular bidimensional tumor area (at lease 50% for lesions \< 1cm, at least 25% for lesions \>=1cm) for any of the 1-3 tracked brain metastases, or the appearance of any new brain metastasis on a follow-up MRI. Progression-free survival was calculated instead of time to progression. Progression-free survival time was measured from registration to the date of progression, death, or last known follow-up (censored). The Kaplan-Meier method used to determine median time (along with 95% confidence intervals).

Outcome measures

Outcome measures
Measure	WBRT With Hippocampal Avoidance n=96 Participants Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Progression-free Survival	5.9 months Interval 4.7 to 8.4

SECONDARY outcome

Timeframe: From start of treatment to 12 months from start of treatment

Population: Eligible patients who started study treatment

For each patient the highest grade adverse event related to treatment was calculated. Those with their highest grade of 3 or higher were counted. Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE

Outcome measures

Outcome measures
Measure	WBRT With Hippocampal Avoidance n=96 Participants Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
The Frequency of Patients With Grade 3 and Higher Adverse Events (AE) Related to Treatment	2 Participants

SECONDARY outcome

Timeframe: Baseline and 4 months from start of treatment

Per the protocol, the feasibility of the proposed translational studies were to be assessed following completion of accrual and sample collection. The decision was made not to pursue this outcome measure. No assays were performed and no data were collected for this Outcome Measure

Outcome measures

Outcome data not reported

Adverse Events

WBRT With Hippocampal Avoidance

Serious events: 13 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	WBRT With Hippocampal Avoidance n=96 participants at risk Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Blood and lymphatic system disorders Anemia	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Cardiac disorders Chest pain - cardiac	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Cardiac disorders Pericardial effusion	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Cardiac disorders Sinus tachycardia	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Colonic perforation	2.1% 2/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Nausea	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Vomiting	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
General disorders Death NOS	2.1% 2/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Infections and infestations Lung infection	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Infections and infestations Sepsis	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Metabolism and nutrition disorders Anorexia	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Metabolism and nutrition disorders Dehydration	2.1% 2/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Cognitive disturbance	2.1% 2/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Dizziness	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Headache	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Nervous system disorders - Other	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Seizure	2.1% 2/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.0% 1/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Vascular disorders Thromboembolic event	2.1% 2/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.

Other adverse events

Other adverse events
Measure	WBRT With Hippocampal Avoidance n=96 participants at risk Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Eye disorders Blurred vision	8.3% 8/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Constipation	5.2% 5/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Nausea	13.5% 13/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Vomiting	6.2% 6/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
General disorders Fatigue	35.4% 34/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
General disorders Gait disturbance	7.3% 7/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Weight loss	7.3% 7/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Metabolism and nutrition disorders Anorexia	13.5% 13/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	5.2% 5/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Dizziness	6.2% 6/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Dysgeusia	6.2% 6/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Headache	17.7% 17/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Memory impairment	10.4% 10/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.2% 6/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Skin and subcutaneous tissue disorders Alopecia	21.9% 21/96 Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.

Additional Information

Wendy Seiferheld, M.S.

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER