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

NCT02953717 | Unknown

• 2 other identifiers: 842003006NTR5463
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

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.

Conditions

Neoplasm Metastasis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  3 months

Secondary Outcomes (12)

• Verbal memory

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

• Cognitive flexibility

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

• Word Fluency

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

• Working memory

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

• Processing speed

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

Study Arms (2)

Stereotactic radiosurgery (SRS)

ACTIVE COMPARATOR

Gamma Knife radiosurgery

Radiation: Gamma Knife radiosurgery

Whole Brain Radiation Therapy (WBRT)

ACTIVE COMPARATOR

Whole Brain Radiation Therapy

Radiation: Whole Brain Radiation Therapy

Interventions

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.

Stereotactic radiosurgery (SRS)

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.

Whole Brain Radiation Therapy (WBRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven malignant cancer
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Elisabeth-TweeSteden Ziekenhuis: lead
• Tilburg University: collaborator
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

Gamma Knife Center Tilburg, Elisabeth-TweeSteden Hospital

Tilburg, North Brabant, 5022 GC, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 29466961 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Brain Neoplasms; Fatigue; Anxiety Disorders; Depression

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Patrick EJ Hanssens, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: November 3, 2016
• Study Start: February 1, 2016
• Primary Completion: July 1, 2023
• Study Completion: December 1, 2023
• Last Updated: September 13, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)