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Radiosurgery Before Surgery for the Treatment of Brain Metastases

Primary Purpose

Metastatic Malignant Neoplasm in the Brain, Metastatic Malignant Solid Neoplasm

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Dexamethasone

Resection

Stereotactic Radiosurgery

About this trial

This is an interventional treatment trial for Metastatic Malignant Neoplasm in the Brain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Emory University Hospital/Winship Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm A (SRS, low dose dexamethasone, surgery)

Arm B (SRS, high dose dexamethasone, surgery)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

Full Information

NCT ID

NCT04895592

First Posted

May 17, 2021

Last Updated

May 1, 2023

Sponsor

Emory University

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04895592

Brief Title

Radiosurgery Before Surgery for the Treatment of Brain Metastases

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 20, 2021 (Actual)

Primary Completion Date

January 31, 2024 (Anticipated)

Study Completion Date

January 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Emory University

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Malignant Neoplasm in the Brain, Metastatic Malignant Solid Neoplasm

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm A (SRS, low dose dexamethasone, surgery)

Arm Type

Experimental

Arm Description

Arm Title

Arm B (SRS, high dose dexamethasone, surgery)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Other Intervention Name(s)

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

Intervention Description

Given PO or IV

Intervention Type

Procedure

Intervention Name(s)

Resection

Other Intervention Name(s)

Surgical Resection

Intervention Description

Undergo surgical resection

Intervention Type

Radiation

Intervention Name(s)

Stereotactic Radiosurgery

Other Intervention Name(s)

Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery

Intervention Description

Undergo SRS

Primary Outcome Measure Information:

Title

Incidence of adverse events grade 3 or greater

Description

Time Frame

At 4 months post-treatment

Secondary Outcome Measure Information:

Title

Density of immune niche in brain metastases

Description

Time Frame

Up to 2 years

Title

Time to local recurrence (LR)

Description

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 Frame

From pre-operative stereotactic radiosurgery (SRS) to intracranial progression at the treated site, assessed up to 2 years

Title

Time to anywhere brain failure (ABF)

Description

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.

Time Frame

From preoperative SRS to intracranial progression at any site within the brain, assessed up to 2 years

Title

Overall survival (OS)

Description

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.

Time Frame

From pre-operative SRS initiation to death, assessed up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zachary Buchwald, MD, PhD

Phone

404-778-1790

zachary.scott.buchwald@emory.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zachary Buchwald, MD, PhD

Organizational Affiliation

Emory University Hospital/Winship Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Emory University Hospital/Winship Cancer Institute

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zachary Buchwald, MD, PhD

Phone

404-778-1790

zachary.scott.buchwald@emory.edu

First Name & Middle Initial & Last Name & Degree

Zachary S. Buchwald, MD, PhD

12. IPD Sharing Statement

Learn more about this trial

Radiosurgery Before Surgery for the Treatment of Brain Metastases

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