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

NCT ID: NCT02953717

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2023-12-31

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.

Conditions

Neoplasm Metastasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stereotactic radiosurgery (SRS)

Gamma Knife radiosurgery

Group Type: ACTIVE_COMPARATOR

Gamma Knife radiosurgery

Intervention Type: 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 (WBRT)

Whole Brain Radiation Therapy

Group Type: ACTIVE_COMPARATOR

Whole Brain Radiation Therapy

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: RADIATION

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tilburg University

OTHER

Sponsor Role: collaborator

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Elisabeth-TweeSteden Ziekenhuis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick EJ Hanssens, MD

Role: PRINCIPAL_INVESTIGATOR

Gamma Knife Center Tilburg, Elisabeth-TweeSteden Hospital, The Netherlands

Locations

Gamma Knife Center Tilburg, Elisabeth-TweeSteden Hospital

Tilburg, North Brabant, Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 29466961 (View on PubMed)

Other Identifiers

NTR5463

Identifier Type: REGISTRY

Identifier Source: secondary_id

842003006

Identifier Type: -

Identifier Source: org_study_id