Phase Ib Study of Stereotactic Radiation and Nivolumab in the Management of Metastatic Breast Cancer Brain Metastases
Overview
- Phase
- Phase 1
- Intervention
- Nivolumab
- Conditions
- Metastatic Breast Cancer
- Sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Number of Participants who experience Dose Limiting Toxicities
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provides signed and dated informed consent
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Age 18 or older
- •Breast cancer with brain metastases, as documented by extracranial tumor biopsy with MRI brain imaging or intracranial surgical pathology revealing brain metastases
- •10 or less brain metastases eligible for SRS to brain metastases or to the post-operative bed
- •Maximum diameter of the largest intact brain metastases ≤ 4 cm
- •Eastern Cooperative Oncology Group performance status 0 to 2
- •Prior treatment with taxane based chemotherapy with anthracyclines (if appropriate)
- •A formalin-fixed, paraffin-embedded tumor tissue block or 10 unstained slides of intracranial/extracranial tumor sample (archival or recent) for biomarker evaluation should be made available and submitted to the central lab for correlative studies. If attempts to obtain archival tissue are unsuccessful the patient may be enrolled.
- •Individuals with prior SRS/fractioned stereotactic radiotherapy (FSRT) treatment will be allowed if active measurable disease has not previously been treated with radiation therapy
Exclusion Criteria
- •Presence of leptomeningeal disease
- •Prior whole brain radiation therapy
- •All toxicities attributed to prior anticancer therapy must have been resolved to Grade 1 (NCI CTCAE Version 5) or baseline before administration of study drug(s) . Some exceptions apply.
- •Women who are pregnant or breastfeeding
- •Active, known, or suspected autoimmune disease. Patients with an autoimmune paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded. Some exceptions apply.
- •Prior therapy with antiPD-1, antiPD-L1, antiPD-L2, antiCD137, or antiCTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
- •Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
- •Any patient requiring supplemental oxygen therapy
- •Patients with prior history of non-breast cancer malignancies are excluded except in the case of adequately treated basal cell cancer, squamous cell skin cancer, chronic lymphocytic leukemia, or other indolent diseases not requiring therapy
- •Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug(s) administration or that would interfere with the interpretation of safety results
Arms & Interventions
Nivolumab followed by stereotactic radiosurgery (SRS)
480 mg Nivolumab will be given intravenously every 4 weeks, followed by SRS the week after the initial dose of Nivolumab.
Intervention: Nivolumab
Nivolumab followed by stereotactic radiosurgery (SRS)
480 mg Nivolumab will be given intravenously every 4 weeks, followed by SRS the week after the initial dose of Nivolumab.
Intervention: Stereotactic Radiosurgery
Outcomes
Primary Outcomes
Number of Participants who experience Dose Limiting Toxicities
Time Frame: Up to 8 weeks
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.
Secondary Outcomes
- Evaluation of intracranial local brain tumor following treatment(At 3, 6 and 12 months post treatment)
- Evaluation of intracranial distant brain tumor following treatment(At 3, 6 and 12 months post treatment)
- Intracranial Progression Free Survival (PFS)(Up to 12 months)
- Extracranial Progression Free Survival (PFS)(Up to 12 months)
- Overall Survival(Up to 24 months)