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NCT Number: NCT02953717

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

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.

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Key information

Conditions

Neoplasm Metastasis Anxiety Disorders Behavior Behavioral Symptoms Brain Diseases Brain Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms Depression Fatigue Mental Disorders Neoplasms Neoplasms by Site Neoplastic Processes Nervous System Diseases Nervous System Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Gamma Knife Center Tilburg, Elisabeth-TweeSteden Hospital

Tilburg, North Brabant, 5022 GC, Netherlands

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Gamma Knife radiosurgery

Radiation

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.

Whole brain radiation therapy

Radiation

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 outcomes

  1. Cognitive decline at 3 months

    Time frame: 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 outcomes

  1. Verbal memory

    Time frame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT

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

  2. Cognitive flexibility

    Time frame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT

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

  3. Word Fluency

    Time frame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT

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

  4. Working memory

    Time frame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT

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

  5. Processing speed

    Time frame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT

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

  6. Motor dexterity

    Time frame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT

    Motor dexterity is measured with the Grooved Pegboard (GP)

  7. Health Related Quality Of Life (HRQOL)

    Time frame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT

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

  8. Fatigue

    Time frame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT

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

  9. Depression and anxiety

    Time frame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT

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

  10. Median Overall Survival

    Time frame: 12 months after GKRS/WBRT

    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.

  11. Local tumor control

    Time frame: 12 months after GKRS/WBRT

    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.

  12. Distant tumor control

    Time frame: 12 months after GKRS/WBRT

    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.

Sponsors and collaborators

Lead sponsor

Elisabeth-TweeSteden Ziekenhuis

Other

Collaborators

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

Registry information

Official study title

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

Important dates

Study start
2016
Primary completion
2023
Study completion
2023
First posted
Nov 3, 2016
Registry last updated
Jun 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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