Radiosurgery Before Surgery for the Treatment of Brain Metastases

Metastatic Malignant Solid Neoplasm Clinical Trial

Official title:

Preoperative Radiosurgery for Brain Metastases Planned for Surgical Resection: A Two Arm Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04895592
• Other study ID #: STUDY00001896
• Secondary ID: NCI-2021-02761ST
• Status: Recruiting
• Phase: Early Phase 1
• Start date: July 20, 2021
• Est. completion date: January 31, 2026

Study information

• Verified date: May 2024
• Source: Emory University
• Contact: Zachary Buchwald, MD, PhD
• Phone: 404-778-1790
• Email: zachary.scott.buchwald[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This early phase I trial identifies the side effects of stereotactic radiosurgery before surgery in treating patients with cancer that has spread to the brain (brain metastases). Radiation may stimulate an anti-tumor immune response. Giving stereotactic radiosurgery before surgery may reduce the risk of the cancer coming back after surgery.

Description:

PRIMARY OBJECTIVE:

I. To determine the safety of pre-operative stereotactic radiosurgery (SRS) followed by surgery for brain metastasis.

SECONDARY OBJECTIVES:

I. To evaluate the immune niche in brain metastasis following SRS in the presence of low or high dose dexamethasone.

II. To evaluate the impact of pre-operative SRS on survival outcomes.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM A: Patients undergo SRS to the brain metastasis for 1-3 fractions over 1-5 days. Patients also receive low dose dexamethasone orally (PO) or intravenously (IV) for 2-21 days until the day of surgical resection. Patients then undergo surgical resection.

ARM B: Patients undergo SRS to the brain metastasis for 1-3 fractions over 1-5 days. Patients also receive high dose dexamethasone PO or IV for 2-21 days until the day of surgical resection. Patients then undergo surgical resection.

After completion of study intervention, patients are followed up for 120 days, and then every 12 weeks thereafter.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 31, 2026
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >= 18 years

• Prior or suspected diagnosis of malignancy

• Brain metastases visible on contrasted magnetic resonance imaging (MRI) brain

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

• Life expectancy > 12 weeks as determined by the investigator

• Patients must have adequate organ function as determined by Neurosurgery to undergo surgery

• Willingness and ability of the subject to comply with scheduled visits, study procedures, and study restrictions

• Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation

• Patient must have a negative pregnancy test, be actively taking oral contraceptives or have undergone a hysterectomy

Exclusion Criteria:

• Patients on any immunosuppressive medication other than dexamethasone

• Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Human immunodeficiency virus (HIV)-positive

• Pregnant or nursing women are excluded

• Prior whole brain radiotherapy or SRS to the same site planned for surgery

Related Conditions & MeSH terms

• Brain Neoplasms
• Metastatic Malignant Neoplasm in the Brain
• Metastatic Malignant Solid Neoplasm
• Neoplasms

Intervention

Drug:
• Dexamethasone
Given PO or IV

Procedure:
• Resection
Undergo surgical resection

Radiation:
• Stereotactic Radiosurgery
Undergo SRS

Locations

Country	Name	City	State
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events grade 3 or greater	Evaluated using Common Terminology Criteria for Adverse Events. Tolerability of this regimen will be defined as < 33% of patients develop grade > 3 at 4 months. Adverse events will be summarized descriptively using frequencies and percentages.	At 4 months post-treatment
Secondary	Density of immune niche in brain metastases	Niche density will be assessed by immunofluorescence as described above. It will be summarized descriptively as the percent of tumor occupied by immune niche for each treatment arm, and will be compared between Arms A and B using a two-sample t-test or non-parametric equivalent, such as Mann-Whitney U test.	Up to 2 years
Secondary	Time to local recurrence (LR)	LR will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median LR will be estimated using the Brookmeyer-Crowley approach.	From pre-operative stereotactic radiosurgery (SRS) to intracranial progression at the treated site, assessed up to 2 years
Secondary	Time to anywhere brain failure (ABF)	ABF will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median TBF will be estimated using the Brookmeyer-Crowley approach.	From preoperative SRS to intracranial progression at any site within the brain, assessed up to 2 years
Secondary	Overall survival (OS)	OS will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median OS will be estimated using the Brookmeyer-Crowley approach.	From pre-operative SRS initiation to death, assessed up to 2 years