Radiosurgery Before Surgery for the Treatment of Brain Metastases

Sponsor

Emory University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04895592

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

18.4

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Malignant Neoplasm in the Brain Metastatic Malignant Solid Neoplasm	Drug: Dexamethasone Procedure: Resection Radiation: Stereotactic Radiosurgery	Early Phase 1

Detailed Description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

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

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 20, 2021

Anticipated Primary Completion Date :

Jan 31, 2023

Anticipated Study Completion Date :

Jan 31, 2023

Arms and Interventions

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: 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 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 Hemady Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex TaperDex Visumetazone ZoDex Procedure: Resection Undergo surgical resection Other Names: Surgical Resection Radiation: Stereotactic Radiosurgery Undergo SRS Other Names: Stereotactic External Beam Irradiation stereotactic external-beam radiation therapy Stereotactic Radiation Therapy Stereotactic Radiotherapy stereotaxic radiation therapy stereotaxic radiosurgery
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.	Procedure: Resection Undergo surgical resection Other Names: Surgical Resection Radiation: Stereotactic Radiosurgery Undergo SRS Other Names: Stereotactic External Beam Irradiation stereotactic external-beam radiation therapy Stereotactic Radiation Therapy Stereotactic Radiotherapy stereotaxic radiation therapy stereotaxic radiosurgery

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:

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

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

Hemady

Hexadecadrol

Hexadrol

Lokalison-F

Loverine

Methylfluorprednisolone

Millicorten

Mymethasone

Orgadrone

Spersadex

TaperDex

Visumetazone

ZoDex

Procedure: Resection

Undergo surgical resection

Other Names:

Surgical Resection

Radiation: Stereotactic Radiosurgery

Undergo SRS

Other Names:

Stereotactic External Beam Irradiation

stereotactic external-beam radiation therapy

Stereotactic Radiation Therapy

Stereotactic Radiotherapy

stereotaxic radiation therapy

stereotaxic radiosurgery

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.

Procedure: Resection

Undergo surgical resection

Other Names:

Surgical Resection

Radiation: Stereotactic Radiosurgery

Undergo SRS

Other Names:

Stereotactic External Beam Irradiation

stereotactic external-beam radiation therapy

Stereotactic Radiation Therapy

Stereotactic Radiotherapy

stereotaxic radiation therapy

stereotaxic radiosurgery

Outcome Measures

Primary Outcome Measures

Incidence of adverse events grade 3 or greater [At 4 months post-treatment]
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.

Secondary Outcome Measures

Density of immune niche in brain metastases [Up to 2 years]
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.
Time to local recurrence (LR) [From pre-operative stereotactic radiosurgery (SRS) to intracranial progression at the treated site, assessed up to 2 years]
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.
Time to anywhere brain failure (ABF) [From preoperative SRS to intracranial progression at any site within the brain, assessed up to 2 years]
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.
Overall survival (OS) [From pre-operative SRS initiation to death, assessed up to 2 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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