Radiosurgery Before Surgery for the Treatment of Brain Metastases

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Malignant Solid Neoplasm; Metastatic Malignant Neoplasm in the Brain
• Intervention / Treatment: Drug: Dexamethasone; Radiation: Stereotactic Radiosurgery; Procedure: Resection

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Zachary Buchwald, MD, PhD; Phone Number: 404-778-1790; Email: zachary.scott.buchwald@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital/Winship Cancer Institute
      • Contact: Zachary Buchwald, MD, PhD; Phone Number: 404-778-1790; Email: zachary.scott.buchwald@emory.edu
      • Principal Investigator: Zachary S. Buchwald, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (SRS, low dose dexamethasone, surgery); Patients undergo SRS to the brain metastasis for 1-3 fractions over 1-5 days. Patients also receive low dose dexamethasone PO or IV for 2-21 days until the day of surgical resection. Patients then undergo surgical resection.	Drug: Dexamethasone; Given PO or IV; Other Names: Decadron; Hemady; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Dxevo; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Radiation: Stereotactic Radiosurgery; Undergo SRS; Other Names: Stereotactic External Beam Irradiation; stereotactic external-beam radiation therapy; Stereotactic Radiotherapy; stereotaxic radiation therapy; stereotaxic radiosurgery; Stereotactic Radiation Therapy; Procedure: Resection; Undergo surgical resection; Other Names: Surgical Resection
Experimental: Arm B (SRS, high dose dexamethasone, surgery); 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.	Radiation: Stereotactic Radiosurgery; Undergo SRS; Other Names: Stereotactic External Beam Irradiation; stereotactic external-beam radiation therapy; Stereotactic Radiotherapy; stereotaxic radiation therapy; stereotaxic radiosurgery; Stereotactic Radiation Therapy; Procedure: Resection; Undergo surgical resection; Other Names: Surgical Resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Zachary Buchwald, MD, PhD, Emory University Hospital/Winship Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Anticipated): January 31, 2024
• Study Completion (Anticipated): January 31, 2025

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: May 1, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Brain Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dermatologic Agents; Dexamethasone; Dexamethasone acetate; BB 1101; Ichthammol
• Other Study ID Numbers: STUDY00001896; P30CA138292 (U.S. NIH Grant/Contract); NCI-2021-02761 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RAD5234-21 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No