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

December 3, 2025 updated by: H. Lee Moffitt Cancer Center and Research Institute

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

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Nivolumab
480 mg intravenous Nivolumab administered every 4 weeks.
Other Names:
  • Opdivo
Radiation: Stereotactic Radiosurgery

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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Up to 8 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Evaluation of intracranial local brain tumor following treatment
Time Frame: At 3, 6 and 12 months post 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.
At 3, 6 and 12 months post treatment
Evaluation of intracranial distant brain tumor following treatment
Time Frame: At 3, 6 and 12 months post treatment
Intracranial distant brain tumor control following SRS and Nivolumab will be determined by the development of new lesions outside of the irradiated area.
At 3, 6 and 12 months post treatment
Intracranial Progression Free Survival (PFS)
Time Frame: Up to 12 months
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.
Up to 12 months
Extracranial Progression Free Survival (PFS)
Time Frame: Up to 12 months
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.
Up to 12 months
Overall Survival
Time Frame: Up to 24 months
Overall Survival defined as time from the date of start of treatment to death.
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bristol-Myers Squibb

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kamran Ahmed, MD, H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 30, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 8, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 18, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 15, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 17, 2019

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 4, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 3, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MCC-19765
  • CA209-8NK (Other Identifier: Bristol-Myers Squibb)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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