Stereotactic Radiation and Nivolumab in the Management of Metastatic Breast Cancer Brain Metastases

H. Lee Moffitt Cancer Center and Research Institute

Status and phase

Active, not recruiting

Phase 1

Conditions

Brain Metastases

Metastatic Breast Cancer

Treatments

Drug: Nivolumab

Radiation: Stereotactic Radiosurgery

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03807765

MCC-19765

CA209-8NK (Other Identifier)

Details and patient eligibility

About

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.

Enrollment

14 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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
Continuing concurrent use of hormonal therapy or HER2-targeted therapy is allowed if the patient exhibits brain metastases progression during treatment
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the administration of each dose of study agent.
WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s), plus 5 half-lives of study drug (half-life up to 25 days), plus 30 days (duration of ovulatory cycle) for a total of 5 months after treatment completion.

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
Major surgery or significant traumatic injury that has not been recovered from by 14 days before the initiation of study drug
Current or prior participation in a study of an investigational agent or investigational device within 2 weeks of first dose of study treatment
Positive test for: a. Hepatitis B virus using Hepatitis B virus surface antigen (Hepatitis B virus surface antigen) test b. Hepatitis C virus (HCV) using HCV ribonucleic acid or HCV antibody test that indicates acute or chronic infection c. Exception: Individuals with a positive test for HCV antibody but no detection of HCV ribonucleic acid indicating no current infection are eligible
Medical history of testing positive for HIV or AIDS. No HIV testing is required, unless mandated by a local health authority.
Inadequate hematologic function
Inadequate hepatic function
Inadequate pancreatic function
History of allergy or hypersensitivity to any of the study drugs or study drug components
Individuals who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness