Metastatic Malignant Neoplasm in the Brain, Metastatic Malignant Solid Neoplasm
Conditions
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.
Interventions
DRUGDexamethasone
Given PO or IV
PROCEDUREResection
Undergo surgical resection
RADIATIONStereotactic Radiosurgery
Undergo SRS
Sponsors
Emory University
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORZachary Buchwald, MD, PhD
Emory University Hospital/Winship Cancer Institute
Outcome results
None listed