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

Neoplasm Metastasis Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02953717
• Other study ID #: 842003006
• Secondary ID: NTR5463
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 2016
• Est. completion date: December 2023

Study information

• Verified date: May 2023
• Source: Elisabeth-TweeSteden Ziekenhuis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 81
• Est. completion date: December 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Brain Neoplasms
• Neoplasm Metastasis

Intervention

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.
• 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.

Locations

Country	Name	City	State
Netherlands	Gamma Knife Center Tilburg, Elisabeth-TweeSteden Hospital	Tilburg	Noord-Brabant

Sponsors (3)

Lead Sponsor	Collaborator
Elisabeth-TweeSteden Ziekenhuis	Tilburg University, ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Verbal memory	Verbal memory is measured with the Hopkins Verbal Learning Test-Revised (HVLT-R)	Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
Secondary	Cognitive flexibility	Cognitive flexibility is measured with the Controlled Oral Word Association (COWA)	Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
Secondary	Word Fluency	Word Fluency is measured with the Controlled Oral Word Association (COWA)	Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
Secondary	Working memory	Working memory is measured with the Wechsler Adult Intelligence Scale - Digit Span	Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
Secondary	Processing speed	Processing speed is measured with the Wechsler Adult Intelligence Scale - Digit Symbol	Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
Secondary	Motor dexterity	Motor dexterity is measured with the Grooved Pegboard (GP)	Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
Secondary	Health Related Quality Of Life (HRQOL)	The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is used to measure HRQOL.	Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
Secondary	Fatigue	Fatigue is measured with the Multidimensional Fatigue Inventory (MFI).	Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
Secondary	Depression and anxiety	Depression and anxiety are measured with the Hospital Anxiety and Depression Scale (HADS).	Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT
Secondary	Median Overall Survival	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.	12 months after GKRS/WBRT
Secondary	Local tumor control	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 months after GKRS/WBRT
Secondary	Distant tumor control	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.	12 months after GKRS/WBRT