Clinical trial NCT04895592: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Metastatic Malignant Neoplasm in the Brain
Metastatic Malignant Solid Neoplasm
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2021-05-20
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of adverse events grade 3 or greater
timeFrame: At 4 months post-treatment
Secondary outcomes:
measure: Density of immune niche in brain metastases
timeFrame: Up to 2 years
measure: Time to local recurrence (LR)
timeFrame: From pre-operative stereotactic radiosurgery (SRS) to intracranial progression at the treated site, assessed up to 2 years
measure: Time to anywhere brain failure (ABF)
timeFrame: From preoperative SRS to intracranial progression at any site within the brain, assessed up to 2 years
measure: Overall survival (OS)
timeFrame: From pre-operative SRS initiation to death, assessed up to 2 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University Hospital/Winship Cancer Institute
name: Zachary Buchwald, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: