A Phase II Study of Pre-Op SRS Followed by Surgical Resection for Brain Metastases

A Phase II Study of Pre-Operative Stereotactic Radiosurgery Followed by Surgical Resection for Brain Metastases

This is a research study to determine if performing stereotactic radiosurgery (SRS) prior to surgical resection of the brain metastasis (tumor) will improve local control, in other words, increase the possibility of total removal of the primary tumor without local recurrence on longterm follow up. This research study will also determine if pre-operative SRS will lower the risk of radionecrosis that is the breakdown of body tissue at the original tumor site, and the development of leptomeningeal disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Brain Metastases, Adult
• Intervention / Treatment: Other: Pre-operative Stereotactic Radiosurgery

Detailed Description

Patients with a solid tumor malignancy that has metastasized to the brain are invited to participate in this trial. Upon enrollment to this study a subject will undergo stereotactic radiosurgery (SRS) using the Elekta Gamma Knife Icon, being treated in once daily 15 minute fractions of 9 Gray (Gy) or every other day 15 minute fractions of 9 Gy for a total dose of 27 Gy in 3 doses. A subject will undergo a routine CT and MRI simulation to determine positioning of the head prior to the start of the SRS treatment. Within two (2) weeks after completion of SRS a subject will undergo a routine surgical resection of the brain metastasis. Prior to the SRS treatment and during the follow up phase of the study MRIs will be performed, which are standard of care. Subjects will also complete a quality of life questionnaire. The duration of subject's time participating in this study is 2 years.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologic proof or unequivocal cytologic proof of solid tumor malignancy. This may be obtained from either the primary site or any metastatic site
2. Solid tumor brain metastases
3. Age≥ 18 years
4. Karnofsky Performance Status ≥70
5. Patient must have agreed to undergo surgical resection to manage at least 1 brain metastasis
6. Maximum tumor diameter of index lesions <5 cm. (Index lesion defined as the brain metastasis which will undergo surgical resection)
7. Brain MRI within 1 month of initiation of brain SRS
8. No prior whole brain radiotherapy (WBRT) or radiation therapy directed to index brain metastases
9. Patients of childbearing potential (male or female) must practice adequate contraception due to possible harmful effects of radiation therapy on an unborn child
10. Patient must have the ability to understand and the willingness to sign a written informed consent document
11. All patients must be informed of the investigational nature of this study and must be given written informed consent in accordance with institutional and federal guidelines
12. Patients receiving prior SRS for brain metastases in other locations of the brain are eligible
13. Patients with multiple brain metastases planned for surgical intervention are eligible for this study. Each individual brain metastasis will be treated

Exclusion Criteria:

1. Prior WBRT or SRS to the index lesion
2. Brain metastasis greater than or equal to (≤) 5 cm in maximum diameter
3. Patients must not have a serious medical or psychiatric illness that would in the opinion of the treating physician prevent informed consent or completion of protocol treatment, and/or follow-up visits.
4. Karnofsky Performance Status (KPS) less than (<)70.
5. Patients with absolute contraindication to MRI imaging are not eligible for the study
6. Patients who are pregnant are excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pre-Operative Stereotactic Radiosurgery (SRS); Subjects are treated using the standard of care SRS to a total dose of 24-27 Gray (Gy) in 3 fractions with a once daily fractionation or every other day at treating physician discretion. The preferred dose will be 27 Gy, with ability to drop dose down to 24 Gy if normal tissue constraints cannot be met. It should be noted, that while the dosing remains within standard of care, the timing of the radiation (pre-operative) is still not considered standard of care but is supported by emerging data as described in the study background. Additional metastatic lesions may be treated using SRS according to institutional practices. The radiation dose prescribed to the non-index lesions is at the discretion of the treating physicians. Surgical resection will be performed within 2 weeks of completion of SRS.

Other: Pre-operative Stereotactic Radiosurgery; Pre-operative SRS will be performed prior to the surgical resection of the brain metastases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Local Control	Radiographic local control at 1 year following completion of pre-operative SRS followed by surgical resection of brain metastasis. Local control will be according to the Response Assessment criteria for Neuro-Oncology (RANO) for brain metastases.	4-5 Years from first subject enrolled.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leptomeningeal disease	MRI will be utilized to evaluate for evidence of leptomeningeal spread at 3 month intervals following preoperative SRS followed by surgical resection of the brain metastasis.	4-5 years from first subject enrolled.
Radio-Necrosis	Pathologic confirmation of radio-necrosis will be recorded as binary variable for each patients as well as the date of surgery confirming radio-necrosis, as applicable.	4-5 years from first subject enrolled
Pseudo-Progression	Defined as worsening T1 post-gadolinium contrast enhancement and fluid attenuated inversion recovery (FLAIR) changes following SRS which resolve independently without any intervention beyond steroids.	4-5 years from first subject enrolled

Collaborators and Investigators

• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Collaborators: Elekta Limited
• Investigators: Principal Investigator: Rodney E Wegner, MD, AHN Radiation Oncology

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2021
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: April 18, 2022
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Stereotactic Radiosurgery (SRS)
• 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: 2021-240-AGH

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