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NTS-WBRT VS HA-WBRT in Brain Metastases

Primary Purpose

Brain Metastases

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

NTS-WBRT (normal tissue sparing whole brain radiation therapy)

HA-WBRT (hippocampal avoidance whole brain radiation therapy)

Memantine

About this trial

This is an interventional treatment trial for Brain Metastases focused on measuring Brain Metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Any patient with a solid tumor diagnosis and any number of brain metastasis clinically indicated for cranial irradiation with whole brain radiation therapy
Age ≥ 18
Karnofsky Performance Status ≥ 70
Prior stereotactic radiosurgery (SRS) permissible per physician discretion
Prior craniotomy permissible per physician discretion. Protocol radiation therapy should be initiated ≥2 weeks after craniotomy.
Prior partial brain radiation therapy permissible if target volume < 50% brain and per physician discretion
Expectant > 6 months survival
Ability to understand and the willingness to sign a written informed consent document.
Fluency in English, able to complete questionnaires and neurocognitive testing
Ability to undergo MRI with gadolinium examination
Ability to return for follow-up examinations throughout the course of this study for a maximum of 2 years after radiation treatment completion
Any prior, concomitant, or post-radiotherapy systemic therapy is permitted at discretion of treating physicians
Negative pregnancy test for premenopausal women

Exclusion Criteria:

Leptomeningeal disease (by any one or more of clinical assessment, radiographic assessment, or cerebrospinal fluid study)
Prior whole brain radiation therapy
Pre-existing or current use of memantine or other NMDA antagonists
Known allergy to contrast used in imaging studies and/or inability to have MRI imaging
Uncontrolled intercurrent illness that could significantly affect baseline cognitive function as determined by the enrolling clinician, such as symptomatic congestive heart failure, unstable angina pectoris, prior CVA, significant uncontrolled epilepsy or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or unwilling to use appropriate contraception to prevent pregnancy during the time of radiation therapy
Concurrent participation in an investigational systemic therapy protocol.

Sites / Locations

Massachusetts General Hospital Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

NTS-WBRT (normal tissue sparing whole brain radiation therapy) + Memantine

HA-WBRT (hippocampal avoidance whole brain radiation Therapy) + Memantine

Arm Description

Participants will be randomly assigned to NTS-WBRT (normal tissue sparing whole brain radiation therapy) administration group and receive: NTS-WBRT for 5 days (Monday-Friday) for either 2 or 3 weeks. Memantine per standard of care, 1-2x daily for up to 24 weeks Specific participant administration schedules will be determined by study doctor

Participants will be randomly assigned to HA-WBRT (hippocampal avoidance whole brain radiation Therapy) administration group and receive: HA-WBRT for 5 days (Monday-Friday) for either 2 or 3 weeks. Memantine per standard of care, 1-2x daily for up to 24 weeks Specific participant administration schedules will be determined by study doctor

Outcomes

Primary Outcome Measures

Change in Patient Reported Quality of Life between NTS-WBRT (normal tissue sparing whole brain radiation therapy) and HA-WBRT (hippocampal avoidance whole brain radiation Therapy)

Assessed by Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. Score range is 0-200 and the higher the score, the better the outcome.

Change in Patient Reported Symptom Burden between NTS-WBRT (normal tissue sparing whole brain radiation therapy) and HA-WBRT (hippocampal avoidance whole brain radiation Therapy)

Assessed by Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. Score range is 0-200 and the higher the score, the better the outcome.

Secondary Outcome Measures

Tumor local control Rates between NTS-WBRT+SIB and HA-WBRT

Estimated by the cumulative incidence function treating death as a competing risk, compared using Gray's test

Intracranial- Progression Free Survival (PFS) between NTS-WBRT+SIB and HA-WBRT

Estimated using the Kaplan-Meier method, compared using the logrank test

Overall survival (OS) between NTS-WBRT+SIB and HA-WBRT

Estimated using the Kaplan-Meier method, compared using the logrank test

Change in Neurocognitive function between NTS-WBRT+SIB and HA-WBRT

Assessed longitudinally by the HADS-D and HADS-A questionnaires

Change in Mood between NTS-WBRT+SIB and HA-WBRT

Mixed effects models with treatment arm as a fixed effect will be used to compare changes in depression (HADS-D) and anxiety (HADS-A) scores over time

Change in Fatigue between NTS-WBRT+SIB and HA-WBRT

Mixed effects models with treatment arm as a fixed effect will be used to compare changes in the fatigue score over time

Change in Neuroendocrine function between NTS-WBRT+SIB and HA-WBRT

Estimated by the cumulative incidence function treating intracranial progression and death as competing risks; compared using Gray's test.

Change in Hearing between NTS-WBRT+SIB and HA-WBRT Assessed by Pure Tone Average

Changes in pure tone average (PTA) from baseline to each subsequent assessment will be compared between treatment arms using Wilcox rank-sum test. Pure tone thresholds are found by presenting tones using standard headphones and methods in a sound treated booth. Pure tone thresholds will be tested by both bone (500, 1000, 2000 and 4000 Hz) and air conduction (250, 500, 1000, 2000, 3000, 4000, 6000, 8000, 10000, 12000, and 14000 Hz). Masking will be applied sufficient to determine the ear responsible for each value. The results of this testing will be used to determine the sensorineural hearing level. If significant conductive loss is found, bone conduction threshold will be used to report sensory ototoxicity. Threshold effects across frequency will be combined into a Pure Tone Average (PTA), defined as the average of audiometric thresholds at 500, 1000, 2000, and 4000. A significant decrease in Pure Tone Average is defined as an increase > 10 dB in relation to baseline threshold.

Change in Hearing between NTS-WBRT+SIB and HA-WBRT Assessed by Word Recognition Score

Changes in word recognition score (WRS) from baseline to each subsequent assessment will be compared between treatment arms using Wilcox rank-sum test. Word recognition is defined as the percent correct on a standard, 50-item word list of English monosyllables: CID W-22, NU#6 or CNC. A significant decrease in word recognition is defined as a score exceeding the 95% critical difference from the table of Thornton and Raffin.

Change in Hearing between NTS-WBRT+SIB and HA-WBRT Assessed by Otoacoustic Emissions

The rates of absent otoacoustic emissions (OAE) will be compared between treatment arms using Fisher's exact test. The OAE (Otoacoustic Emissions) test checks part of the inner ear's response to sound. Otoacoustic emissions are sounds given off by one small part of the cochlea when it is stimulated by soft clicking sounds. When the sound stimulates the cochlea, the outer hair cells vibrate. The vibration produces a nearly inaudible sound that echoes back into the middle ear. The results are either present or absent. Present OAEs are consistent with normal to near normal hearing. Absent OAEs may be a sign of a problem related to study treatment.

Alopecia Rates between NTS-WBRT+SIB and HA-WBRT

Assessed by patient report and visual inspection with documented photography; compared by Fisher's exact test

Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0

The number and proportion of adverse events, graded as defined by CTCAE version 5.0 will be tabulated by type and grade, compared using Fisher's exact test.

Full Information

NCT ID

NCT05013892

First Posted

August 6, 2021

Last Updated

April 7, 2022

Sponsor

Massachusetts General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05013892

Brief Title

NTS-WBRT VS HA-WBRT in Brain Metastases

Official Title

Randomized Phase II Trial of Normal Tissue Sparing Whole Brain Radiation Therapy (NTS-WBRT) Versus Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT) in Patients With Brain Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

February 8, 2022 (Actual)

Primary Completion Date

December 31, 2025 (Anticipated)

Study Completion Date

December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This research is being done to compare quality of life and symptom burden in participants who receive two different types of radiation therapy (normal tissue sparing whole brain radiation therapy (NTS-WBRT) or standard of care hippocampal avoidance whole brain radiation Therapy (HA-WBRT). This research study involves: NTS-WBRT (normal tissue sparing whole brain radiation therapy) HA-WBRT (hippocampal avoidance whole brain radiation Therapy) Memantine standard of care drug

Detailed Description

This is a Phase 2 randomized trial testing the safety and effectiveness of NTS-WBRT (normal tissue sparing whole brain radiation therapy) as compared to HA-WBRT (hippocampal avoidance whole brain radiation Therapy) in treating brain metastases. NTS-WBRT is a targeted radiation therapy that further reduces radiation dose to tissue that does not need radiation therapy treatment. HA-WBRT is a targeted radiation therapy that avoids the hippocampus (part of the brain that controls learning and memory) tissue during radiation therapy treatment. The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. It is expected that about 100 people will take part in this research study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brain Metastases

Keywords

Brain Metastases

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

NTS-WBRT (normal tissue sparing whole brain radiation therapy) + Memantine

Arm Type

Experimental

Arm Description

Arm Title

HA-WBRT (hippocampal avoidance whole brain radiation Therapy) + Memantine

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

NTS-WBRT (normal tissue sparing whole brain radiation therapy)

Other Intervention Name(s)

Radiation Therapy

Intervention Description

Radiation

Intervention Type

Radiation

Intervention Name(s)

HA-WBRT (hippocampal avoidance whole brain radiation therapy)

Other Intervention Name(s)

Radiation Therapy

Intervention Description

Radiation

Intervention Type

Drug

Intervention Name(s)

Memantine

Other Intervention Name(s)

Namenda, Namenda XR, Namenda XR Titration Pack

Intervention Description

Capsule, taken orally

Primary Outcome Measure Information:

Title

Change in Patient Reported Quality of Life between NTS-WBRT (normal tissue sparing whole brain radiation therapy) and HA-WBRT (hippocampal avoidance whole brain radiation Therapy)

Description

Assessed by Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. Score range is 0-200 and the higher the score, the better the outcome.

Time Frame

4 Months

Title

Change in Patient Reported Symptom Burden between NTS-WBRT (normal tissue sparing whole brain radiation therapy) and HA-WBRT (hippocampal avoidance whole brain radiation Therapy)

Description

Assessed by Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. Score range is 0-200 and the higher the score, the better the outcome.

Time Frame

4 Months

Secondary Outcome Measure Information:

Title

Tumor local control Rates between NTS-WBRT+SIB and HA-WBRT

Description

Estimated by the cumulative incidence function treating death as a competing risk, compared using Gray's test

Time Frame

baseline, 2, 4, 6, 9, 12, 18 and 24 months

Title

Intracranial- Progression Free Survival (PFS) between NTS-WBRT+SIB and HA-WBRT

Description

Estimated using the Kaplan-Meier method, compared using the logrank test

Time Frame

baseline, 2, 4, 6, 9, 12, 18 and 24 months

Title

Overall survival (OS) between NTS-WBRT+SIB and HA-WBRT

Description

Estimated using the Kaplan-Meier method, compared using the logrank test

Time Frame

The date of randomization to the date of death, or otherwise censored at the last follow-up date for patients still alive up to 24 months

Title

Change in Neurocognitive function between NTS-WBRT+SIB and HA-WBRT

Description

Assessed longitudinally by the HADS-D and HADS-A questionnaires

Time Frame

baseline, 2, 4, 6, 9, 12, 18 and 24 months

Title

Change in Mood between NTS-WBRT+SIB and HA-WBRT

Description

Mixed effects models with treatment arm as a fixed effect will be used to compare changes in depression (HADS-D) and anxiety (HADS-A) scores over time

Time Frame

baseline, 2, 4, 6, 9, 12, 18 and 24 months

Title

Change in Fatigue between NTS-WBRT+SIB and HA-WBRT

Description

Mixed effects models with treatment arm as a fixed effect will be used to compare changes in the fatigue score over time

Time Frame

baseline, 2, 4, 6, 9, 12, 18 and 24 months

Title

Change in Neuroendocrine function between NTS-WBRT+SIB and HA-WBRT

Description

Estimated by the cumulative incidence function treating intracranial progression and death as competing risks; compared using Gray's test.

Time Frame

baseline, 2, 4, 6, 9, 12, 18 and 24 months

Title

Change in Hearing between NTS-WBRT+SIB and HA-WBRT Assessed by Pure Tone Average

Description

Time Frame

baseline, 2, 4, 6, 9, 12, 18 and 24 months

Title

Change in Hearing between NTS-WBRT+SIB and HA-WBRT Assessed by Word Recognition Score

Description

Time Frame

baseline, 2, 4, 6, 9, 12, 18 and 24 months

Title

Change in Hearing between NTS-WBRT+SIB and HA-WBRT Assessed by Otoacoustic Emissions

Description

Time Frame

baseline, 2, 4, 6, 9, 12, 18 and 24 months

Title

Alopecia Rates between NTS-WBRT+SIB and HA-WBRT

Description

Assessed by patient report and visual inspection with documented photography; compared by Fisher's exact test

Time Frame

baseline, 2, 4, 6, 9, 12, 18 and 24 months

Title

Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0

Description

The number and proportion of adverse events, graded as defined by CTCAE version 5.0 will be tabulated by type and grade, compared using Fisher's exact test.

Time Frame

Up to 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Any patient with a solid tumor diagnosis and any number of brain metastasis clinically indicated for cranial irradiation with whole brain radiation therapy Age ≥ 18 Karnofsky Performance Status ≥ 70 Prior stereotactic radiosurgery (SRS) permissible per physician discretion Prior craniotomy permissible per physician discretion. Protocol radiation therapy should be initiated ≥2 weeks after craniotomy. Prior partial brain radiation therapy permissible if target volume < 50% brain and per physician discretion Expectant > 6 months survival Ability to understand and the willingness to sign a written informed consent document. Fluency in English, able to complete questionnaires and neurocognitive testing Ability to undergo MRI with gadolinium examination Ability to return for follow-up examinations throughout the course of this study for a maximum of 2 years after radiation treatment completion Any prior, concomitant, or post-radiotherapy systemic therapy is permitted at discretion of treating physicians Negative pregnancy test for premenopausal women Exclusion Criteria: Leptomeningeal disease (by any one or more of clinical assessment, radiographic assessment, or cerebrospinal fluid study) Prior whole brain radiation therapy Pre-existing or current use of memantine or other NMDA antagonists Known allergy to contrast used in imaging studies and/or inability to have MRI imaging Uncontrolled intercurrent illness that could significantly affect baseline cognitive function as determined by the enrolling clinician, such as symptomatic congestive heart failure, unstable angina pectoris, prior CVA, significant uncontrolled epilepsy or psychiatric illness/social situations that would limit compliance with study requirements Pregnant or unwilling to use appropriate contraception to prevent pregnancy during the time of radiation therapy Concurrent participation in an investigational systemic therapy protocol.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Helen A Shih, MD, MS, MPH

Phone

(617) 724-9627

hshih@mgh.harvard.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Helen A Shih, MD, MS, MPH

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital Cancer Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Helen A Shih, MD,MS,MPH

Phone

617-724-9627

hshih@mgh.harvard.edu

First Name & Middle Initial & Last Name & Degree

Helen A Shih, MD, MS, MPH

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

IPD Sharing Time Frame

Data can be shared no earlier than 1 year following the date of publication

IPD Sharing Access Criteria

Contact the Partners Innovations team at http://www.partners.org/innovation

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NTS-WBRT VS HA-WBRT in Brain Metastases

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