This study is to find out if administration of stereotactic radiosurgery (SRS) given after Nivolumab will improve overall response rate/anti-tumor activity in patients with metastatic breast cancer with brain metastases.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
14
480 mg intravenous Nivolumab administered every 4 weeks.
Patients will receive single session SRS to intact brain metastases and post-operative cavities. A linear accelerator (LINAC)-based frameless delivery system will be used to deliver the stereotactic radiation. The lesion will be defined using gadolinium enhanced MRI with 1 mm slices for treatment planning purposes prior to the delivery of radiation. The MRI image will be co-registered and fused with CT imaging. Doses will be prescribed to ensure coverage of at least 95% of the planning target volume (PTV) with the prescription dose. Treatments will be delivered using dynamic conformal arcs or intensity modulated radiotherapy.
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Number of Participants who experience Dose Limiting Toxicities
Neurologic dose limiting toxicities will be defined as: Symptomatic radionecrosis, \>/= Grade 3 headache, \>/= Grade 3 memory impairment, New onset \>/= grade 3 seizures. 3 participants will be enrolled with an 8 week safety observation period. If no patients develop unacceptable neurologic toxicity attributable to SRS, the study will proceed. If 1 patient develops unacceptable neurologic toxicity among the first 3, an additional 3 patients will be enrolled to determine the rate of unacceptable toxicity with 6 patients. If no more patients develop unacceptable neurologic toxicities among the first 6 patients, the study will proceed with a dose expansion of 6 patients. If 2 or more patients develop unacceptable neurologic toxicity among the first 3 or 6 patients, the dose of radiation therapy will be adjusted. If excessive toxicities are noted with radiation dose level -1, treatment will proceed with nivolumab alone.
Time frame: Up to 8 weeks
Evaluation of intracranial local brain tumor following treatment
Intracranial local brain tumor control following SRS and Nivolumab will be determined from irradiated lesions according to Response Assessment in Neuro-Oncology (RANO) criteria.
Time frame: At 3, 6 and 12 months post treatment
Evaluation of intracranial distant brain tumor following treatment
Intracranial distant brain tumor control following SRS and Nivolumab will be determined by the development of new lesions outside of the irradiated area.
Time frame: At 3, 6 and 12 months post treatment
Intracranial Progression Free Survival (PFS)
Time from the date of start of treatment to the investigator-determined date of progression (determined by RANO) or death due to any cause, whichever occurs first.
Time frame: Up to 12 months
Extracranial Progression Free Survival (PFS)
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Time from the date of start of treatment to the investigator determined date of progression (determined by Immune-Related Response Evaluation Criteria in Solid Tumors \[irRECIST\]) or death due to any cause, whichever occurs first.
Time frame: Up to 12 months
Overall Survival
Overall Survival defined as time from the date of start of treatment to death.
Time frame: Up to 24 months