Clinical trial NCT02953717: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Neoplasm Metastasis
Keywords: Brain metastases
Cognition
Radiosurgery
Gamma Knife Radiosurgery
Stereotactic radiosurgery
Whole Brain Radiation Therapy
Quality of Life
Fatigue
Anxiety
Depression
Lead sponsor: Elisabeth-TweeSteden Ziekenhuis
Sponsor class: OTHER
Collaborators: name: Tilburg University
name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2016-11-03
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Cognitive decline at 3 months
timeFrame: 3 months
Secondary outcomes:
measure: Verbal memory
timeFrame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
measure: Cognitive flexibility
timeFrame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
measure: Word Fluency
timeFrame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
measure: Working memory
timeFrame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
measure: Processing speed
timeFrame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
measure: Motor dexterity
timeFrame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
measure: Health Related Quality Of Life (HRQOL)
timeFrame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
measure: Fatigue
timeFrame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
measure: Depression and anxiety
timeFrame: Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
measure: Median Overall Survival
timeFrame: 12 months after GKRS/WBRT
measure: Local tumor control
timeFrame: 12 months after GKRS/WBRT
measure: Distant tumor control
timeFrame: 12 months after GKRS/WBRT
Other outcomes:
Locations:
city: Tilburg
country: Netherlands
facility: Gamma Knife Center Tilburg, Elisabeth-TweeSteden Hospital
state: Noord-Brabant
Study officials:
affiliation: Gamma Knife Center Tilburg, Elisabeth-TweeSteden Hospital, The Netherlands
name: Patrick EJ Hanssens, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schimmel WCM, Verhaak E, Hanssens PEJ, Gehring K, Sitskoorn MM. A randomised trial to compare cognitive outcome after gamma knife radiosurgery versus whole brain radiation therapy in patients with multiple brain metastases: research protocol CAR-study B. BMC Cancer. 2018 Feb 21;18(1):218. doi: 10.1186/s12885-018-4106-2.