SIMT Stereotactic Radiosurgery Outcomes Study

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02886572
• Collaborator: Varian Medical Systems (Industry)
• Enrollment: 40
• Location: 1
• Arm: 1
• Actual Duration (Months): 51.1
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Brain Metastases, Adult	Radiation: Stereotactic radiosurgery	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jan 25, 2017
• Actual Primary Completion Date: Apr 30, 2021
• Actual Study Completion Date: Apr 30, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Live Longer Than Predicted According to the Graded Prognostic Assessment (GPA) Score [Up to 24 months after SRS]

   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.

Secondary Outcome Measures

1. Number of Participants Who Experience Local Brain Recurrence Within 1 Year of SIMT SRS Treatment [Up to 12 months after SRS]

   Local recurrence of brain metastases is based on serial MRIs every 3 months and estimated by Kaplan-Meier analysis.

2. Number of Participants Who Are Dead Within 1 Year of SIMT SRS Treatment Due to Neurologic Reasons [Up to 12 months after SRS]

   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.

3. 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 [Up to 12 months after SRS]

   Distant recurrence of brain metastases is based on serial MRIs every 3 months and estimated by Kaplan-Meier analysis.

4. Number of Participants Who Experience Grade 3, 4, or 5 Neurologic Adverse Events Attributable to SIMT SRS [Up to 12 months after SRS]

   Adverse Events only included those that were deemed by the PI to be related to the SIMT SRS treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University
• Varian Medical Systems

Investigators

• Principal Investigator: Grace J. Kim, MD PhD, Duke University Medical Center, Radiation Onoclogy

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 21, 2017

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02886572
• Other Study ID Numbers: Pro00075429
• First Posted: Sep 1, 2016
• Last Update Posted: Jun 1, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasm Metastasis; Brain Neoplasms

Study Results

Participant Flow

Arm/Group Title	Stereotactic Radiosurgery
Arm/Group Description	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 Stereotactic radiosurgery: Linear-accelerator-based, single-isocenter, image-guided stereotactic radiosurgery
Period Title: Overall Study
STARTED	40
Survival Analysis Population	40
Distant Brain Recurrence	32
Local Recurrence	32
Time to Neurologic Death	32
SRS Related Adverse Events	32
COMPLETED	32
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Stereotactic Radiosurgery
Arm/Group Description	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 Stereotactic radiosurgery: Linear-accelerator-based, single-isocenter, image-guided stereotactic radiosurgery
Overall Participants	40
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	25 62.5%
Male	15 37.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.5%
Not Hispanic or Latino	38 95%
Unknown or Not Reported	1 2.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 17.5%
White	33 82.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Karnofsky performance status (units on a scale (percentage)) [Median (Full Range) ]
Median (Full Range) [units on a scale (percentage)]	90
Number of Metastases per participant (metastases) [Median (Full Range) ]
Median (Full Range) [metastases]	6
Prior brain surgery for metastasis (Count of Participants)
Count of Participants [Participants]	36 90%
Prior stereotactic radiosurgery or whole brain radiation (Count of Participants)
Count of Participants [Participants]	11 27.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Live Longer Than Predicted According to the Graded Prognostic Assessment (GPA) Score
Description	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.
Time Frame	Up to 24 months after SRS

Outcome Measure Data

Analysis Population Description

Participants who completed the study.

Arm/Group Title	Stereotactic Radiosurgery
Arm/Group Description	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 Stereotactic radiosurgery: Linear-accelerator-based, single-isocenter, image-guided stereotactic radiosurgery
Measure Participants	32
Count of Participants [Participants]	22 55%

2. Secondary Outcome

Title	Number of Participants Who Experience Local Brain Recurrence Within 1 Year of SIMT SRS Treatment
Description	Local recurrence of brain metastases is based on serial MRIs every 3 months and estimated by Kaplan-Meier analysis.
Time Frame	Up to 12 months after SRS

Outcome Measure Data

Analysis Population Description

Participants who completed the study.

Arm/Group Title	Stereotactic Radiosurgery
Arm/Group Description	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 Stereotactic radiosurgery: Linear-accelerator-based, single-isocenter, image-guided stereotactic radiosurgery
Measure Participants	32
Count of Participants [Participants]	4 10%

3. Secondary Outcome

Title	Number of Participants Who Are Dead Within 1 Year of SIMT SRS Treatment Due to Neurologic Reasons
Description	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.
Time Frame	Up to 12 months after SRS

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stereotactic Radiosurgery
Arm/Group Description	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 Stereotactic radiosurgery: Linear-accelerator-based, single-isocenter, image-guided stereotactic radiosurgery
Measure Participants	40
Count of Participants [Participants]	30 75%

4. Secondary Outcome

Title	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
Description	Distant recurrence of brain metastases is based on serial MRIs every 3 months and estimated by Kaplan-Meier analysis.
Time Frame	Up to 12 months after SRS

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stereotactic Radiosurgery
Arm/Group Description	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 Stereotactic radiosurgery: Linear-accelerator-based, single-isocenter, image-guided stereotactic radiosurgery
Measure Participants	40
Count of Participants [Participants]	19 47.5%

5. Secondary Outcome

Title	Number of Participants Who Experience Grade 3, 4, or 5 Neurologic Adverse Events Attributable to SIMT SRS
Description	Adverse Events only included those that were deemed by the PI to be related to the SIMT SRS treatment.
Time Frame	Up to 12 months after SRS

Outcome Measure Data

Analysis Population Description

Participants who completed the study.

Arm/Group Title	Stereotactic Radiosurgery
Arm/Group Description	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 Stereotactic radiosurgery: Linear-accelerator-based, single-isocenter, image-guided stereotactic radiosurgery
Measure Participants	32
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	Serious Adverse Events were only collected if they were grade 3, 4, or 5 event and were deemed by the Principal Investigator to be probably, possibly, or definitely related to the SRS treatment.
Arm/Group Title	Stereotactic Radiosurgery
Arm/Group Description	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 Stereotactic radiosurgery: Linear-accelerator-based, single-isocenter, image-guided stereotactic radiosurgery
All Cause Mortality
	Stereotactic Radiosurgery
	Affected / at Risk (%)	# Events
Total	39/40 (97.5%)
Serious Adverse Events
	Stereotactic Radiosurgery
	Affected / at Risk (%)	# Events
Total	0/40 (0%)
Other (Not Including Serious) Adverse Events
	Stereotactic Radiosurgery
	Affected / at Risk (%)	# Events
Total	16/40 (40%)
Eye disorders
Eye disorders: other, specify (decrease visual acuity)	2/40 (5%)	2
Gastrointestinal disorders
Nausa	10/40 (25%)	10
Vomiting	2/40 (5%)	2
General disorders
Gait disturbance	3/40 (7.5%)	3
Nervous system disorders
Headache	16/40 (40%)	16
Dizziness	2/40 (5%)	2
Memory impairment	3/40 (7.5%)	3
Skin and subcutaneous tissue disorders
Alopecia	8/40 (20%)	8
Scalp pain	3/40 (7.5%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.