SIMT Stereotactic Radiosurgery Outcomes Study (SIMT)

Outcome in Patients With 4 or More Brain Metastases Treated With Single-Isocenter, Multi-Target (SIMT) Stereotactic Radiosurgery: A Prospective Single-arm Study in Adults With Brain Metastases

The purpose of this study is to determine the effectiveness and efficiency of Single Isocenter Multi-target Stereotactic Radiosurgery (SIMT SRS) in patients with four or more brain metastases

Study Overview

• Status: Completed
• Conditions: Brain Metastases, Adult
• Intervention / Treatment: Radiation: Stereotactic radiosurgery

Detailed Description

Forty patients with four or more brain metastases will be enrolled prior to radiosurgery. A planning MRI brain scan will be performed with GD-DPTA within one week prior to radiosurgery, per the standard of care. Neurocognitive (Mini-Mental Status Examination (MMSE), Trail-making test A&B, Hopkins Learning Verbal (HVLT)) and functional assessment of cancer therapy-brain (FACT- Br) will be obtained prior to radiosurgery. Dose will be prescribed to the maximum isodose line encompassing the resulting PTV using the dose guidelines as described below.

The primary endpoint will be the proportion of patients who live longer than predicted based on the diagnosis-specific GPA score. The Kaplan-Meier estimator will be used to describe the survival of all patients treated with SIMT SRS. Secondary endpoints will be the rate of recurrence at the treated metastases sites, the rate of new brain metastases at a site different from the SRS-treated metastases sites, the rate of death due to neurological causes, and the prevalence of significant adverse events. Exploratory endpoints include change over time in neurocognition and quality of life, quantification of dosimetric measures, the rate of salvage therapy, the rate of radionecrosis at the SRS treatment sites, and the rate and intensity of steroid-usage post-SRS.

All patients will be evaluated for neurocognitive function via MMSE, HVLT, and Trail-making tests A & B, quality of life via FACT-Br, and for local recurrence via MRI every 3 months over the course of the study. These evaluations will be done at regular follow-up evaluations or when local recurrence is suspected on the basis of symptoms. Distant recurrence is defined as the appearance of new brain metastases at a site different from that of the original metastases. Recurrence will further be defined as a new area of enhancement that measures greater than 5 millimeters in the axial plane on MRI. The length of time to recurrence of the original brain metastases will be calculated from the date of the brain metastases radiosurgery to the date that a recurrence was detected by MRI. Patients with suspected recurrent tumor and/or who are symptomatic may undergo a stereotactic biopsy to evaluate for radionecrosis versus recurrent brain metastases, as is standard of care.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. A contrast-enhanced MRI scan showing = or > 4 brain metastases.
2. Age >/=18 years of age.
3. KPS >/= 70
4. Patient must have a graded prosnostic score (GPA) score 0.5 or greater
5. Life expectancy of at least 3 months
6. Postoperative patients with resected brain metastases are eligible.
7. Largest lesion < 4cm diameter
8. Must be a candidate for MRI imaging
9. Previous cranial stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) is allowed if > 3 months prior to SIMT
10. Must be capable of providing informed consent

Exclusion Criteria:

1. Primary lesion with radiosensitive histology (i.e., small cell carcinoma, germ-cell tumors, lymphoma, leukemia, and multiple myeloma).
2. Metastases within 2 mm of the optic apparatus
3. Patients unable to obtain MRI
4. Evidence of leptomeningeal disease
5. Greater than 10 brain metastases
6. Pregnant women are excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stereotactic Radiosurgery; All subjects will receive stereotactic radiosurgery(SRS) following the RTOG Stereotactic Radiotherapy Guidelines available at http://dx.doi.org/10.1016/j.prro.2011.06.014	Radiation: Stereotactic radiosurgery; Linear-accelerator-based, single-isocenter, image-guided stereotactic radiosurgery; Other Names: SRS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Live Longer Than Predicted According to the Graded Prognostic Assessment (GPA) Score	Calculated from the time of protocol Stereotactic RadioSurgery (SRS). The GPA incorporates four factors: age, KPS (Karnofsky Performance Score), ECM (extracranial metastases) and number of BM (brain metastases). Each factor is given a score of 0, 0.5 or 1.0 and GPA is calculated as a sum score of all four factors. The GPA has four groups: the GPA 0-1 with median survival of 2.6 months; GPA 1.5-2.5 with survival of 3.8 months; GPA 3 with median survival of 6.9 months and GPA 3.5-4.0 with the best median survival of 11 months.	Up to 24 months after SRS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience Local Brain Recurrence Within 1 Year of SIMT SRS Treatment	Local recurrence of brain metastases is based on serial MRIs every 3 months and estimated by Kaplan-Meier analysis.	Up to 12 months after SRS
Number of Participants Who Are Dead Within 1 Year of SIMT SRS Treatment Due to Neurologic Reasons	Time to neurologic death is defined as the time between initiation of SIMT SRS and death due to neurologic causes and is estimated using Kaplan-Meier analysis.	Up to 12 months after SRS
Number of Participants Who Experience a New Brain Metastasis at a Site Different From the Original Brain Metastasis Site 1 Year After SIMT SRS Treatment	Distant recurrence of brain metastases is based on serial MRIs every 3 months and estimated by Kaplan-Meier analysis.	Up to 12 months after SRS
Number of Participants Who Experience Grade 3, 4, or 5 Neurologic Adverse Events Attributable to SIMT SRS	Adverse Events only included those that were deemed by the PI to be related to the SIMT SRS treatment.	Up to 12 months after SRS

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Varian Medical Systems
• Investigators: Principal Investigator: Grace J. Kim, MD PhD, Duke University Medical Center, Radiation Onoclogy

Publications and helpful links

General Publications

• Kim GJ, Buckley ED, Herndon JE, Allen KJ, Dale TS, Adamson JD, Lay L, Giles WM, Rodrigues AE, Wang Z, Kelsey CR, Torok JA Jr, Chino JP, Fecci PE, Sampson JH, Anders CK, Floyd SR, Yin FF, Kirkpatrick JP. Outcomes in Patients With 4 to 10 Brain Metastases Treated With Dose-Adapted Single-Isocenter Multitarget Stereotactic Radiosurgery: A Prospective Study. Adv Radiat Oncol. 2021 Jul 23;6(6):100760. doi: 10.1016/j.adro.2021.100760. eCollection 2021 Nov-Dec.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2017
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): April 30, 2021

Study Registration Dates

• First Submitted: August 29, 2016
• First Submitted That Met QC Criteria: August 31, 2016
• First Posted (Estimate): September 1, 2016

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: Pro00075429

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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