This trial will be a randomized controlled study comparing the efficacy and safety of intraoperative radiation therapy using GammaTilesTM (GT) versus SRT 3-4 weeks following metastatic tumor resection which is the current standard of care.
GammaTile therapy results in improved clinical outcomes; however, the data is a single site experience with a limited number of subjects, including only 12 of which were patients with metastatic brain tumors. The primary objective of this randomized, controlled trial is to compare the efficacy and safety of intraoperative radiation therapy using GammaTile® (GT) versus SRT 3-4 weeks following metastatic tumor resection which is the current standard of care. The data collected in this trial design will allow for a direct comparison of a variety of outcomes including local control, overall survival, functional status, quality of life, neurocognitive status, and safety in the target population. In order to support direct comparisons, subjects will be randomized to the two equally sized arms (1:1) based on the following stratification factors: age (\<60 vs ≥60), duration of extracranial disease control (≤3 months vs \>3 months), number of metastases (one, 2-4 total, 5-6 total ), histology (breast cancer, lung cancer, melanoma, other), the maximal diameter of the index lesion (≤3 cm, \>3 cm to ≤5cm, \>5cm to ≤7cm) and use of prior or current immunotherapy (yes vs no). An index lesion meeting the criteria of ≥ 2.0-7.0 cm in maximum diameter and appropriate for gross total resection (GTR), will be identified and up to five (5) other unresected, previously untreated lesions in a patient will be allowed. After resection of the index lesion, the surgical bed will be treated with adjunct radiation (either GT or SRT) thereby following the standard of care guidelines (NCCN Guidelines, 2019). Additionally, all unresected, previously untreated metastatic lesions will be treated with stereotactic radiosurgery alone, which also adheres to standard of care guidelines (NCCN Guidelines, 2019). GammaTile is an FDA-cleared means of rapid dose delivery of radiation therapy directly to the tumor bed with predictable dosimetry at the immediate time of resection, and an intense but localized radiation treatment may confer a reduced risk for radiation necrosis compared to other therapies. It is typically easily placed with minimal additional operative time and limited staff radiation exposure. Given these benefits, the rationale for conducting this randomized controlled comparison study is to generate additional data, to further support the use of this new FDA-cleared method of delivering radiation therapy in the setting of newly diagnosed brain metastases.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
230
GammaTiles are a permanently implanted radiation device consisting of Cs-131 seeds positioned within a collagen tile
External Beam Radiation Therapy
Surgical bed recurrence-free survival (SB-RFS) from the time of randomization up to 2 years post radiation.
Surgical bed control is defined as the absence of new nodular contrast enhancement in the index lesion surgical bed.
Time frame: up to 2 years post-radiation
Overall Survival
Survival of subjects
Time frame: up to 3 years
Functional Assessment of Cancer Therapy-Brain (FACT-Br)
An assessment of quality of life (QOL)
Time frame: up to 9 months
Linear Analog Scale Assessments (LASA)
An assessment of quality of life (QOL)
Time frame: up to 9 months
Hopkins Verbal Learning Test (HVLT-R)
An assessment of neurocognitive status
Time frame: up to 24 months
Controlled Oral Word Association Test (COWAT)
An assessment of neurocognitive status
Time frame: up to 24 months
Trail Making Tests (TMT) Parts A and B
An assessment of neurocognitive status
Time frame: up to 24 months
Barthel ADL
An assessment of physical functioning status
Time frame: up to 24 months
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