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Metastatic Breast CancerPhase 1NCT03807765

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

A Phase 1 study testing Nivolumab and Stereotactic Radiosurgery in people with Metastatic Breast Cancer and Brain Metastases, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer, Brain Metastases
What is being tested?
Nivolumab and Stereotactic Radiosurgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
30 Jan 2019to 18 Mar 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: 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.

Being tested
Nivolumab, Stereotactic Radiosurgery
Keywords
breast cancer, brain metastases
Medical subject headings
Breast Neoplasms, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Opdivo

    480 mg intravenous Nivolumab administered every 4 weeks.

  • Stereotactic RadiosurgeryRadiation

    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.

Study groups in NCT03807765
Study groupRoleWhat they receive
Nivolumab followed by stereotactic radiosurgery (SRS)Experimental480 mg Nivolumab will be given intravenously every 4 weeks, followed by SRS the week after the initial dose of Nivolumab.
Receives: Drug: Nivolumab; Radiation: Stereotactic Radiosurgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 8 weeks

Secondary outcomes (5)

  1. 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.

    Measured: At 3, 6 and 12 months post treatment

  2. 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.

    Measured: At 3, 6 and 12 months post treatment

  3. 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.

    Measured: Up to 12 months

  4. Extracranial Progression Free Survival (PFS)

    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.

    Measured: Up to 12 months

  5. Overall Survival

    Overall Survival defined as time from the date of start of treatment to death.

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jan 2019
  2. Study start30 Jan 2019
  3. Primary completion8 Sep 2020
  4. Study completion18 Mar 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03807765
Sponsor's protocol ID
MCC-19765
Other IDs
CA209-8NK
Status last verified
Dec 2025
First submitted
15 Jan 2019
Last updated
4 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Ahmed KA, Kim Y, Kim S, Wang MH, DeJesus M, Arrington JA, Soyano AE, Armaghani AJ, Costa RLB, Loftus LS, Rosa M, Caudell JJ, Diaz R, Etame AB, Tran ND, Soliman H, Czerniecki BJ, Forsyth PA, Yu HM, Han HS. Nivolumab and stereotactic radiosurgery for patients with breast cancer brain metastases: long-term results and biomarker analysis from a non-randomized, open-label, phase Ib study. J Immunother Cancer. 2025 Apr 28;13(4):e011432. doi: 10.1136/jitc-2024-011432.

    PubMed 40295143

  • Ahmed KA, Kim Y, Arrington JA, Kim S, DeJesus M, Soyano AE, Armaghani AJ, Costa RLB, Khong HT, Loftus LS, Rosa M, Caudell JJ, Diaz R, Robinson TJ, Etame AB, Tran ND, Sahebjam S, Soliman HH, Czerniecki BJ, Forsyth PA, Yu HM, Han HS. Nivolumab and Stereotactic Radiosurgery for Patients With Breast Cancer Brain Metastases: A Nonrandomized, Open-Label Phase 1b Study. Adv Radiat Oncol. 2021 Sep 11;6(6):100798. doi: 10.1016/j.adro.2021.100798. eCollection 2021 Nov-Dec.

    PubMed 34934864

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nivolumab and Stereotactic Radiosurgery in people with Metastatic Breast Cancer and Brain Metastases, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants who experience Dose Limiting Toxicities (time frame: Up to 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03807765, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2025.

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