Pre- Versus Post-operative SRS for Resectable Brain Metastases

A Randomized Controlled Trial of Pre-operative Versus Post-operative Stereotactic Radiosurgery for Patients With Surgically Resectable Brain Metastases

The purpose of this study is to determine if performing radiotherapy (SRS) prior to surgery results in better treatment outcomes than performing surgery before radiotherapy for patients with brain metastases.

Brain metastases occur when cancer cells from a primary cancer (e.g. lung, breast, colon) travel through the bloodstream and spread (metastasize) to the brain. As these new tumors grow they apply pressure and change how healthy brain tissue works. This can lead to a loss of brain function and worsening quality of life. Treatments for patients whose cancer has spread to the brain is often surgery, radiation therapy (radiotherapy) or a combination of both.

Surgery is one the main treatments for brain tumors. To remove the tumor, a neurosurgeon makes an opening in the skull and attempts to the remove the entire tumor. If the tumor is too close to important brain tissue, the surgeon may attempt to remove part of the tumor. Removal of the tumor from the brain tissue is called resection. The complete or partial removal of tumor helps to relieve symptoms by reducing pressure on healthy tissues and reduces the amount of tumor that needs to be treated by radiotherapy.

One type of radiotherapy used to treat brain metastases is stereotactic radiosurgery (SRS). SRS uses many focused radiation beams to treat tumors within the brain. Unlike surgery, there is no incision or cut being made. Instead, SRS uses an accurate map of your brain to deliver a precise beam of radiation to the tumors. The radiation damages the tumor cells forcing them to shrink and die off. The focused radiation beams also limit damage to healthy brain tissue minimizing side effects.

Surgery followed by radiotherapy is a standard treatment for brain metastases. However, there are still risks associated with the combination of treatments. This study plans to investigate whether performing surgery prior to SRS results in improved quality of life and decreased side effects.

Study Overview

• Status: Terminated
• Conditions: Brain Metastases
• Intervention / Treatment: Procedure: Brain Surgery; Radiation: Stereotactic Radiosurgery

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Tom Baker Cancer Centre/Arthur J.E. Child Comprehensive Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Pathologically-proven primary malignancy
• ECOG 0-2
• Ability to complete neurocognitive testing without assistance from family or friends.
• Previous SRS to lesions other than the one being resected is allowed
• Patients of childbearing / reproductive potential must have a negative urine or serum pregnancy test ≤7 days before enrollment
• Participants capable of giving informed consent, or if appropriate participants having an acceptable individual capable of giving consent

Exclusion Criteria:

• Patients who have received prior WBRT, or SRS to the lesion being resected at time of study accrual
• Patients unable to undergo MRI scan (e.g. pacemaker)
• Leptomeningeal disease
• Germ cell tumor, small cell lung cancer or hematological primary malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Surgical Resection followed by SRS (Non-Experimental); Surgical Resection followed by SRS within 3 weeks of surgery date.	Procedure: Brain Surgery; Surgery to remove brain metastases; Radiation: Stereotactic Radiosurgery; SRS uses many focused radiation beams to treat tumors within the brain; Other Names: SRS
Experimental: SRS followed by Surgical Resection (Experimental); SRS followed by surgery within 1 week of radiotherapy end date.	Procedure: Brain Surgery; Surgery to remove brain metastases; Radiation: Stereotactic Radiosurgery; SRS uses many focused radiation beams to treat tumors within the brain; Other Names: SRS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Control	To compare local control (in months) of pre-operative versus post-operative SRS	This will be assessed at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Control	To compare local control (in months) of pre-operative versus post-operative SRS	This will be assessed at 6 and 24 months.
Distant Brain Recurrence Rate	To compare Distant Brain Recurrence Rate (%) of pre-operative versus post-operative SRS	This will be assessed at 6,12 and 24 months.
Leptomeningeal Recurrence Rate	To compare the Leptomeningeal Recurrence Rate (%) of pre-operative versus post-operative SRS	This will be assessed at 6,12 and 24 months.
Overall Survival	Overall survival will be compared between both treatment arms	This will be assessed at 6,12 and 24 months.
Hopkins Verbal Learning Test	Participants are scored using a points based system on Total Recall, Delayed Recall, Retention (% retained), and a Recognition Discrimination Index.	This will be assessed at 3,6,9,12,16 and 24 months.
Controlled Oral Word Association	Participants are scored on their ability to generate words starting with a specific letter in a one minute timeframe.	This will be assessed at 3,6,9,12,16 and 24 months.
Trial Making Tests	Participants are scored on their ability to complete the test within a certain timeframe.	This will be assessed at 3,6,9,12,16 and 24 months.

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2021
• Primary Completion (Actual): April 7, 2025
• Study Completion (Actual): April 7, 2025

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: July 14, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Actual): July 18, 2025
• Last Update Submitted That Met QC Criteria: July 16, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Neurosurgery; Stereotactic Radiosurgery
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: IIT-0010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No