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Cognitive Outcome After SRS or WBRT in Patients With Multiple Brain Metastases (CAR-Study B)

Primary Purpose

Neoplasm Metastasis

Status

Active

Phase

Not Applicable

Locations

Netherlands

Study Type

Interventional

Intervention

Gamma Knife radiosurgery

Whole Brain Radiation Therapy

About this trial

This is an interventional treatment trial for Neoplasm Metastasis focused on measuring Brain metastases, Cognition, Radiosurgery, Gamma Knife Radiosurgery, Stereotactic radiosurgery, Whole Brain Radiation Therapy, Quality of Life, Fatigue, Anxiety, Depression

Eligibility Criteria

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

Inclusion Criteria:

Histologically proven malignant cancer
11-20 newly diagnosed brain metastases on a triple dose gadolinium-enhanced MRI-scan
Maximum total tumor volume ≤ 30 cm3
Lesion ≥ 3 mm from the optic apparatus
Age ≥ 18 years
Karnofsky Performance Status (KPS) ≥ 70
Anticipated survival > 3 months

Exclusion Criteria:

No prior histologic confirmation of malignancy
Primary brain tumor
A second active primary tumor
Small cell lung cancer (SCLC)
Lymphoma
Leukemia
Meningeal disease
Progressive, symptomatic systemic disease without further treatment options
Prior brain radiation
Prior surgical resection of BM
Cardiovascular accident (CVA) < 2 years ago
Additional history of a significant neurological or psychiatric disorder
Contra indications to MRI or gadolinium contrast
Underlying medical condition precluding adequate follow-up
Participation in a concurrent study in which neuropsychological testing and/or health-related QOL assessments are involved
Lack of basic proficiency in Dutch
IQ below 85
Severe aphasia
Paralysis grade 0-3 according to MRC scale (Medical Research Council)

Sites / Locations

Gamma Knife Center Tilburg, Elisabeth-TweeSteden Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Stereotactic radiosurgery (SRS)

Whole Brain Radiation Therapy (WBRT)

Arm Description

Gamma Knife radiosurgery

Whole Brain Radiation Therapy

Outcomes

Primary Outcome Measures

Cognitive decline at 3 months

Cognitive decline is defined as a significant decline (5 point decrease from baseline based on the Reliable Change Index (RCI) with correction for practice effects) in HVLT-R Total Recall score (verbal learning and memory test) after treatment with either GKRS or WBRT in patients with 11-20 brain metastases at time of treatment initiation.

Secondary Outcome Measures

Verbal memory

Verbal memory is measured with the Hopkins Verbal Learning Test-Revised (HVLT-R)

Cognitive flexibility

Cognitive flexibility is measured with the Controlled Oral Word Association (COWA)

Word Fluency

Word Fluency is measured with the Controlled Oral Word Association (COWA)

Working memory

Working memory is measured with the Wechsler Adult Intelligence Scale - Digit Span

Processing speed

Processing speed is measured with the Wechsler Adult Intelligence Scale - Digit Symbol

Motor dexterity

Motor dexterity is measured with the Grooved Pegboard (GP)

Health Related Quality Of Life (HRQOL)

The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is used to measure HRQOL.

Fatigue

Fatigue is measured with the Multidimensional Fatigue Inventory (MFI).

Depression and anxiety

Depression and anxiety are measured with the Hospital Anxiety and Depression Scale (HADS).

Median Overall Survival

Overall survival is defined as the time in months from the start of treatment to the date of death or last contact if alive. Kaplan-Meier methods are used to estimate overall survival.

Local tumor control

Local brain tumor control of the initial treated lesions is defined as a complete, partial, or stable response, or less than a 25% increase in diameter on contrast-enhanced MRI follow-up and not requiring resection. Any initial treated lesions increased by more than 25% in diameter on contrast-enhanced MRI or required resection will be considered a local failure.

Distant tumor control

Distant brain tumor control is defined as the absence of any new brain metastases, distinct from the initial treated lesion(s), on follow-up MRI. The appearance of one or more new lesions in the brain by contrast-enhanced follow-up MRI is considered distant failure.

Full Information

NCT ID

NCT02953717

First Posted

October 27, 2016

Last Updated

September 11, 2023

Sponsor

Elisabeth-TweeSteden Ziekenhuis

Collaborators

Tilburg University, ZonMw: The Netherlands Organisation for Health Research and Development

1. Study Identification

Unique Protocol Identification Number

NCT02953717

Brief Title

Cognitive Outcome After SRS or WBRT in Patients With Multiple Brain Metastases (CAR-Study B)

Official Title

A Prospective Randomized Study to Compare Cognitive Outcome After Stereotactic Radiosurgery or Whole Brain Radiation Therapy in Patients With 11-20 Brain Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 2016 (undefined)

Primary Completion Date

July 2023 (Actual)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Elisabeth-TweeSteden Ziekenhuis

Collaborators

Tilburg University, ZonMw: The Netherlands Organisation for Health Research and Development

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Whole Brain Radiation Therapy (WBRT) has long been the mainstay of treatment for patients with multiple brain metastases (BM). Meanwhile, Gamma Knife radiosurgery (GKRS) has been increasingly employed in the management of multiple BM to spare healthy tissue. Hence, GKRS is expected to cause fewer cognitive side effects than WBRT. Treatment of multiple BM without cognitive side effects is becoming more important, as more patients live longer due to better systemic treatment options. There are no published randomized trials yet directly comparing GKRS to WBRT in patients with multiple BM, including objective neuropsychological testing. CAR-Study B is a prospective randomized trial comparing cognitive outcome after GKRS or WBRT in eligible patients with 11-20 BM.

Detailed Description

CAR-Study B is a prospective randomized trial comparing cognitive outcome after GKRS or WBRT in eligible patients with 11-20 BM on a triple dose gadolinium-enhanced MRI-scan. Neuropsychological assessment will be performed at baseline and at 3, 6, 9, 12 and 15 months after treatment. Follow-up assessments will be combined with 3-monthly MRI-scans. Patients will be randomized to either GKRS or WBRT. Groups will be balanced at baseline (prior to radiotherapy), taking into account several (stratification) factors that may influence cognitive functioning over time, such as: total tumor volume in the brain, systemic treatment, KPS, age, histology, and baseline HVLT-R total recall score.

6. Conditions and Keywords

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

Neoplasm Metastasis

Keywords

Brain metastases, Cognition, Radiosurgery, Gamma Knife Radiosurgery, Stereotactic radiosurgery, Whole Brain Radiation Therapy, Quality of Life, Fatigue, Anxiety, Depression

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

81 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Stereotactic radiosurgery (SRS)

Arm Type

Active Comparator

Arm Description

Gamma Knife radiosurgery

Arm Title

Whole Brain Radiation Therapy (WBRT)

Arm Type

Active Comparator

Arm Description

Whole Brain Radiation Therapy

Intervention Type

Radiation

Intervention Name(s)

Gamma Knife radiosurgery

Intervention Description

GKRS is performed with a Leksell Gamma Knife® Icon, Elekta Instruments, AB. Depending upon the volume, a dose of 18-25 Gy will be prescribed with 99-100% coverage of the target.

Intervention Type

Radiation

Intervention Name(s)

Whole Brain Radiation Therapy

Intervention Description

Patients in the WBRT group will receive 4 Gy x 5 fractions (total of 20 Gy) in one week, which is a commonly utilized treatment schedule according to Dutch guidelines.

Primary Outcome Measure Information:

Title

Cognitive decline at 3 months

Description

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Verbal memory

Description

Verbal memory is measured with the Hopkins Verbal Learning Test-Revised (HVLT-R)

Time Frame