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

This study is currently recruiting participants.
Verified November 2016 by Elisabeth-TweeSteden Ziekenhuis
Sponsor:
ClinicalTrials.gov Identifier:
NCT02953717
First Posted: November 3, 2016
Last Update Posted: November 3, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
University of Tilburg
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Elisabeth-TweeSteden Ziekenhuis
  Purpose

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.


Condition Intervention
Neoplasm Metastasis Radiation: Gamma Knife radiosurgery Radiation: Whole Brain Radiation Therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Further study details as provided by Elisabeth-TweeSteden Ziekenhuis:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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)

  • 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)

  • 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)

  • 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

  • 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

  • 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)

  • 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.

  • Fatigue [ Time Frame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT ]
    Fatigue is measured with the Multidimensional Fatigue Inventory (MFI).

  • 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).

  • 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.

  • 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.

  • 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.


Estimated Enrollment: 80
Study Start Date: February 2016
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Stereotactic radiosurgery (SRS)
Gamma Knife radiosurgery
Radiation: Gamma Knife radiosurgery
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.
Active Comparator: Whole Brain Radiation Therapy (WBRT)
Whole Brain Radiation Therapy
Radiation: Whole Brain Radiation Therapy
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.

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02953717


Contacts
Contact: Wietske CM Schimmel, MSc. +31 135391333 w.schimmel@etz.nl
Contact: Eline Verhaak, MSc. +31 135391333 e.verhaak@etz.nl

Locations
Netherlands
Gamma Knife Center Tilburg, Elisabeth-TweeSteden Hospital Recruiting
Tilburg, Noord-Brabant, Netherlands, 5022 GC
Contact: Patrick EJ Hanssens, MD    +31 135392543    p.hanssens@etz.nl   
Sponsors and Collaborators
Elisabeth-TweeSteden Ziekenhuis
University of Tilburg
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Principal Investigator: Patrick EJ Hanssens, MD Gamma Knife Center Tilburg, Elisabeth-TweeSteden Hospital, The Netherlands
  More Information

Responsible Party: Elisabeth-TweeSteden Ziekenhuis
ClinicalTrials.gov Identifier: NCT02953717     History of Changes
Other Study ID Numbers: 842003006
NTR5463 ( Registry Identifier: Netherlands Trail Register )
First Submitted: October 27, 2016
First Posted: November 3, 2016
Last Update Posted: November 3, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Elisabeth-TweeSteden Ziekenhuis:
Brain metastases
Cognition
Radiosurgery
Gamma Knife Radiosurgery
Stereotactic radiosurgery
Whole Brain Radiation Therapy
Quality of Life
Fatigue
Anxiety
Depression

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Neoplastic Processes
Neoplasms
Pathologic Processes