AzTrials
AzTrials

Breast CancerPhase 2NCT03483012

Atezolizumab + Stereotactic Radiation in Triple-negative Breast Cancer and Brain Metastasis

A Phase 2 study testing Atezolizumab and Stereotactic radiosurgery (SRS) in people with Breast Cancer, run by Dana-Farber Cancer 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
Search all trials

Trial summary

This research study is studying the combination of a drug called atezolizumab and a radiation procedure called stereotactic radiosurgery (SRS) as a possible treatment for triple-negative breast cancer that has spread to the brain. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Atezolizumab and Stereotactic radiosurgery (SRS)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
1 May 2018to 12 Nov 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have histologically or cytologically confirmed Stage IV invasive breast cancer. Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
  • Either the primary tumor and/or metastatic tumor must be triple-negative as defined below:
  • Hormone receptor status: the invasive tumor must be ER- and PR-negative, or staining present in <1% by immunohistochemistry (IHC)
  • HER2 status: the invasive tumor must be Human Epidermal Growth Factor Receptor 2 Negative (HER2-negative) by the ASCO CAP guidelines
  • In cases where both primary tumor and metastatic sample(s) have been tested for ER, PR, and HER2, the triple-negative status of the most recent sample should be used.
  • Participants must have a diagnosis of brain metastases for which SRS is indicated, as determined by a radiation oncologist.
Show all 31Show fewer
  • The contrast-enhancing intraparenchymal brain metastases(s) must be well circumscribed and must have a maximum diameter of ≤ 3.0 cm in any direction on the enhanced scan.
  • Participants must not have more than 5 new or progressive lesions in the brain requiring SRS treatment (greater than 5 total brain lesions are allowed as long as no more than 5 lesions require SRS treatment).
  • Participants must have measurable extracranial disease as defined by RECIST 1.1.
  • Participants must be willing to undergo a research biopsy at baseline and at Cycle 2 Day 1 if extracranial metastases are safely accessible. Participants for whom biopsies cannot be safely performed must be willing to submit an archival primary and/or metastatic specimen. The biopsies may be waived with prior PI approval for the first 6 participants enrolled to the safety run in phase.
  • Prior systemic therapy:
  • Participants must have discontinued systemic therapy at least 14 days prior to initiating protocol therapy.
  • There is no limit to the number of prior lines of systemic therapy. Participants who have not received any systemic therapy for metastatic disease are also eligible.
  • Participants may initiate or continue bisphosphonate therapy on study.
  • Prior local therapy:
  • Prior surgery, whole brain radiation or SRS is allowed as long as the most recent brain progression is amenable to SRS treatment.
  • Resolution of all chemotherapy-related or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (≤ Grade 2 allowed) and alopecia (of any grade).
  • Participant is ≥18 years old.
  • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
  • Stable dose of dexamethasone 2mg or less for at least 7 days prior to initiation of treatment
  • Participants must have normal organ and marrow function as defined below:
  • absolute neutrophil count ≥1,000/μl
  • platelets ≥75,000/μl
  • hemoglobin ≥9 g/dL
  • total bilirubin ≤1.5mg/dL (≤2.0 in patients with known Gilberts syndrome)
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN. ≤5.0 × institutional ULN for patients with documented liver metastases.
  • albumin >2.5mg/dL
  • serum creatinine ≤1.5mg/dL or calculated GFR ≥60 mL/min
  • Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 8 days of initiating protocol therapy.
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. The effects of atezolizumab on the developing human fetus are unknown and radiotherapy has known teratogenic effects so women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after completion of atezolizumab administration.
  • The subject is capable of understanding and complying with the protocol and has signed the informed consent document

Who cannot join

  • CNS complications for whom urgent neurosurgical intervention is indicated (e.g., resection, shunt placement).
  • Known leptomeningeal or brainstem metastases. The presence of leptomeningeal enhancement alone, without associated clinical manifestations and/or positive CSF cytology, will not be constituted as known leptomeningeal metastases.
  • Treatment with high dose systemic corticosteroids defined as dexamethasone >2mg/day or bioequivalent within 7 days of initiating therapy.
  • Patients unable to undergo gadolinium contrast-enhanced MRI or receive IV contrast for any reason (e.g., due to pacemaker, ferromagnetic implants, claustrophobia, extreme obesity, hypersensitity).
  • Participants who are receiving any other investigational agents.
  • Previous treatment with any anti-PD-1, PD-L1, or PD-L2 agent.
Show all 15Show fewer
  • Subjects with a history of hypersensitivity to compounds of similar biologic composition to atezolizumab or any constituent of the product
  • The participant has an uncontrolled intercurrent illness, including, but not limited to uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure-New York Heart Association Class III or IV, active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, gastric or duodenal ulceration diagnosed within the previous 6 months, severe malnutrition or psychiatric illness/social situations that would limit compliance with study requirements.
  • Participant has a medical condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication. For example, patients with autoimmune disease that requires systemic steroids or immunosuppression agents should be excluded. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has evidence of active, noninfectious pneumonitis that requires treatment with steroids.
  • Has a history of interstitial lung disease.
  • The participant is known to be positive for the human immunodeficiency virus (HIV), HepBsAg, or HCV RNA. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with atezolizumab.
  • Individuals with a history of different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years or are deemed by the principal investigator to be at low risk for recurrence of that malignancy.
  • Has received a live vaccine within 28 days of planned start of study therapy.
  • The participant is pregnant or breast-feeding.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase II Study of Atezolizumab in Combination With Stereotactic Radiation for Patients With Triple-negative Breast Cancer and Brain Metastasis

This research study is studying the combination of a drug called atezolizumab and a radiation procedure called stereotactic radiosurgery (SRS) as a possible treatment for triple-negative breast cancer that has spread to the brain.

The interventions involved in this study are:

  • Atezolizumab
  • Stereotactic radiosurgery (SRS)
Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved atezolizumab for this specific disease but it has been approved for other uses.

Atezolizumab is a protein that affects the immune system by blocking the PD-L1 pathway. The PD-L1 pathway controls the body's natural immune response, but tumors can interrupt this pathway and partially resist or escape the immune system. By blocking the PD-L1 pathway, Atezolizumab may help the immune system identify and catch tumor cells.

Stereotactic radiosurgery (SRS) is a standard procedure used to treat patients with cancer in the brain. SRS uses many precisely focused radiation beams to treat tumors. It is not surgery in the traditional sense because there's no incision. Instead, SRS uses 3-D imaging to target high doses of radiation to the affected area with minimal impact on the surrounding healthy tissue. Like other forms of radiation, SRS works by damaging the DNA of the targeted (tumor) cells. The affected cells then lose the ability to reproduce, which causes tumors to shrink.

When given separately, atezolizumab and SRS, work in different ways to help stop cancer cells from growing and spreading. However, it is not known if giving atezolizumab and SRS at the same time will have a better effect than giving each treatment on its own. It is hoped that SRS treatment will damage cancer cells and make them more visible to the immune system.

The researchers conducting this study are testing to see whether giving SRS with atezolizumab may boost the body's immune response to cancer, and therefore improve upon the effects of either SRS or atezolizumab given alone.

In this research study, the investigators will measure the length of time that the participant receive this study intervention without the disease getting worse. The investigators will also look at how well the disease responds to atezolizumab and SRS as well as the safety of the combination.

Conditions
Breast Cancer
Being tested
Atezolizumab, Stereotactic radiosurgery (SRS)
Keywords
Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

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

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab is a protein that affects your immune system by blocking the PD-L1 pathway

  • Stereotactic radiosurgery (SRS)Procedure or surgery

    Stereotactic radiosurgery (SRS) is a standard procedure used to treat patients with cancer in the brain. SRS uses many precisely focused radiation beams to treat tumors

Study groups in NCT03483012
Study groupRoleWhat they receive
Atezolizumab + Stereotactic radiosurgery (SRS)Experimental* Atezolizumab administered intravenously once every 3 weeks * Stereotactic radiosurgery (SRS) begin within 14 days after brain MRI obtained
Receives: Drug: Atezolizumab; Procedure: Stereotactic radiosurgery (SRS)

What is being measured

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

  1. Progression-Free Survival

    Defined as time from first dose of atezolizumab (day 1 cycle 1) to progression or death due to any cause. Progression is defined according to the bi-compartmental model proposed in the RANO-BM publication, and is defined as the first detection of radiologic progression of intracranial (per RANO-BM criteria), extracranial (per RECIST 1.1 criteria), or both or unequivocal progression of non-measurable disease in the opinion of the treating physician; with each compartment (CNS and non-CNS) assessed separately

    Measured: Assessed from the first dose of atezolizumab until the date of first documented progression according to RANO-BM or date of death from any cause, whichever came first, for a maximum of 1.5 years

Secondary outcomes (2)

  1. Extracranial Objective Response Rate

    Defined as the percentage of patients achieving a complete response (complete disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits [i.e., "non-CR/non-PD" in non-target lesions]; and no new lesions) based on RECIST 1.1

    Measured: Assessed from the first dose of atezolizumab until disease progression, intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, for a maximum of 1.5 years

  2. Overall Survival

    Defined as the time from first dose of atezolizumab (day 1 cycle 1) to death from any cause. Patients who are alive at the end of the study are censored at the date of last known alive.

    Measured: Assessed from the first dose of atezolizumab to the date of death from any cause or date last known alive, for a maximum of 3.8 years

Timeline

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

  1. First posted29 Mar 2018
  2. Study start1 May 2018
  3. Primary completion21 Nov 2019
  4. Study completion12 Nov 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03483012
Sponsor's protocol ID
17-519
Status last verified
Mar 2026
First submitted
28 Feb 2018
Last updated
21 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Giordano A, Graham N, Aizer AA, Tayob N, Pereslete AM, Schoenfeld JD, Leone JP, Davis R, Erick TK, Mayer EL, Winer EP, Krop I, Tolaney SM, Lin NU. A phase II study of atezolizumab in combination with stereotactic radiation for patients with triple-negative breast cancer and brain metastasis. Breast Cancer Res Treat. 2026 Mar 7;216(2):24. doi: 10.1007/s10549-026-07932-6.

    PubMed 41793510

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab and Stereotactic radiosurgery (SRS) in people with Breast Cancer, run by Dana-Farber Cancer 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 31 inclusion and 15 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 21 Apr 2026. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Progression-Free Survival (time frame: Assessed from the first dose of atezolizumab until the date of first documented progression according to RANO-BM or date of death from any cause, whichever came first, for a maximum of 1.5 years). 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 NCT03483012, which also lists 1 linked publication.

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 21 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in