Frameless Stereotactic Radiosurgery for Intact Brain Metastases

Study Overview
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Brief Summary
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This is a randomized study to determine if not treating planning target volume (PTV) margins during radiation therapy worsens progression free survival rates in patients with brain metastases.

Official Title
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The Clinical Relevance of Margins in Frameless Stereotactic Radiosurgery for Intact Brain Metastases: a Randomized Trial of 0 vs 2 mm Margins

Conditions
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Brain Metastases

Intervention / Treatment
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* Procedure: Stereotactic Radiosurgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (≥ 18 years old) with an ECOG Performance Status 0-2 and a life expectancy of 3 months or more. Histologically confirmed systemic malignancy with gadolinium contrast-enhanced MRI scan demonstrating 1-5 intraparenchymal brain metastases. Well-circumscribed, measureable intraparenchymal brain lesion(s) with maximum tumor diameter ≤3.0 cm. If multiple lesions are present, the other(s) must not exceed 3.0 cm in maximum diameter. At least one lesion must be ≥1.0 cm in maximum diameter and ≥0.5 cm in a perpendicular diameter to be considered measurable disease. Negative urine or serum pregnancy test done ≤ 14 days prior to CT simulation, for women of child-bearing potential only. Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: Diagnosis of germ cell tumor, small cell carcinoma or hematologic malignancy. Metastases in the brain stem, midbrain, pons, medulla, or within 7 mm of the optic apparatus (optic nerves, chiasm and optic tracts). Diagnosis of leptomeningeal disease. Prior cranial radiotherapy within 90 days of trial enrollment or prior SRS at any time to any lesion to be treated on protocol Chemotherapy (including oral agents and targeted agents) or immunotherapy given within 14 days of SRS. Hormonal therapy is permitted. For Her2+ breast cancer patients, anti-Her2 therapy cannot be given within 14 days of SRS. Patients who are scheduled to receive trastuzumab emtansine after SRS cannot be enrolled. Contraindications to gadolinium contrast-enhanced MRI (eg, non-compatible pacemaker, eGFR<30, gadolinium allergy).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stereotactic Radiosurgery to 2 mm GTV to PTV margins<br> | Procedure: Stereotactic Radiosurgery<br>* The SRS dose will depend on the maximum diameter of the gross tumor volume (GTV)<br>|
| Experimental: Stereotactic Radiosurgery to 0 mm GTV to PTV margins<br> | Procedure: Stereotactic Radiosurgery<br>* The SRS dose will depend on the maximum diameter of the gross tumor volume (GTV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) rates estimated by the Kaplan-Meier method at 6 months |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) rates estimated by the Kaplan-Meier method |  | 2 years | 
| Overall survival rates |  | 6 years | 
| Rates of radiation necrosis |  | 2 years | 
| Rates of pseudoprogression |  | 2 years | 
| Local failure rates |  | 2 years | 
| Rate of acute central nervous system (CNS) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 2 and higher toxicities |  | 90 days | 
| Rate of late central nervous system (CNS) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 2 and higher toxicities |  | 6 years | 
| Rates of distant intracranial failure |  | 2 years | 
| Rates of salvage therapy |  | 2 years | 
| Association between dose and risk of radionecrosis or pseudoprogression |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain metastases, Stereotactic Radiosurgery