Clinical trial NCT02729558: Local Radiotherapy Following Complete Resection of a Brain Metastasis
Official title: Postoperative Local Stereotactic Radiotherapy Versus Observation Following a Complete Resection of a Single Brain Metastasis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Brain Neoplasms
Keywords: brain metastases
radiotherapy
resection
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: The Netherlands Cancer Institute
name: UMC Utrecht
First posted: 2016-04-06
Enrollment: 70
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: Objective: To improve local control following complete resection of a single brain metastasis using fractionated local stereotactic radiotherapy, whilst maintaining neurological functioning, neurocognition and quality of life.

Study design: Multicenter randomized phase III, with at least three high-volume Dutch centers participating in the trial. Stratification on primary tumor type and age.

Study population: Patients undergoing complete resection of a single brain metastasis, confirmed by an early (i.e. within 72 hours) postoperative contrast-enhanced MR scan.

Study intervention: Patients will be randomized between observation alone (standard arm) and local stereotactic radiotherapy in three fractions of 8 Gy to the surgical cavity (study arm).

Main study parameters: Primary objective: local control rate at 6 months. Secondary objectives: local control rate at 12 months, neurological functioning, freedom from clinical neurological progression, performance status, quality of life, toxicity, steroid use, neurocognition and overall survival.

Detailed description: The objective of this study is to improve local control following complete resection of a single brain metastasis of solid tumors using fractionated local stereotactic radiotherapy, whilst maintaining neurological functioning, neurocognition and quality of life. The study is performed in the form of a multicenter randomized phase III, with at least three high-volume Dutch centers participating in the trial. Stratification will be performed on primary tumor type and age. A total of 70 patients will be included. Inclusion is restricted to patients who underwent a complete resection of a single brain metastasis, confirmed by an early (i.e. within 72 hours) postoperative contrast-enhanced magnetic resonance (MR) scan. Patients will be randomized between observation alone (standard arm) and local stereotactic radiotherapy in three fractions of 8 Gy to the surgical cavity (study arm).The main study parameters are: local control rate at 6 months (primary outcome measure) and local control rate at 12 months, neurological functioning, freedom from clinical neurological progression, performance status, quality of life, toxicity, steroid use, neurocognition and overall survival (secondary outcome measures). Follow up will be performed at three-monthly interval during the first two years, including MRI scans. Quality of life questionaires and neurocognitive functioning tests will be performed at fixed intervals during follow-up.

Eligibility criteria: Inclusion Criteria:

* Age of 18 years or older.
* Radiologically confirmed complete resection of a single brain metastasis on a contrast-enhanced MRI within 72 h after resection.
* Primary solid tumor, excluding hematologic malignancy, germ cell tumor, small cell lung cancer.
* Stable extracranial tumor (primary tumor and/or systemic metastases) during the last three months with or without treatment or progressive extracranial tumor and/or systemic metastases for which effective treatment is available.
* World Health Organization (WHO) performance score 0-2.
* Ability to provide written informed consent.

Exclusion Criteria:

* Prior treatment for brain metastases (i.e. surgery, stereotactic radiotherapy or WBRT).
* Distant brain metastases or radiological findings on MRI suspected for leptomeningeal tumor spread on the postoperative MRI.
* Concurrent use of systemic therapy during local stereotactic radiotherapy

Primary outcomes:
measure: local control rate
timeFrame: at 6 months
Secondary outcomes:
measure: Decrease in neurocognitive test results using the Hopkins Verbal Learning Test Revised (HVLT-R), in full cohorts
timeFrame: baseline, at 3 months, 6 months and 12 months
measure: Decrease in specified neurocognitive test results using the Trail Making A and B, in full cohorts
timeFrame: baseline, at 3 months, 6 months and 12 months
measure: Decrease in neurocognitive test results using the Controlled Oral Word Association (COWA), in full cohorts
timeFrame: baseline, at 3 months, 6 months and 12 months
measure: Decrease in neurocognitive test results using using the Wechsler Adult Intelligence Scale (WAIS) III Digit Span and WAIS III Digit Symbol, in full cohorts
timeFrame: baseline, at 3 months, 6 months and 12 months
measure: Decrease in neurocognitive test results using the Grooved Pegboard, in full cohorts
timeFrame: baseline, at 3 months, 6 months and 12 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek
city: Amsterdam
country: Netherlands
facility: VU University medical center
Study officials:
References: