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Breast Cancer (Advanced/Metastatic)Phase 2HERBRAINNCT07905313

Study of Trastuzumab Deruxtecan in Combination With Stereotactic Radiosurgery in Patients With HER2-Positive Metastatic Breast Cancer and First Diagnosis of Brain Metastases (HERBRAIN)

A Phase 2 study testing SRS/fSRT+T-Dxd in people with Breast Cancer (Advanced/Metastatic), run by Azienda Ospedaliero-Universitaria Careggi.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

This is a Phase II, single-arm, Bayesian adaptive trial. The study employs a two-stage design with an interim analysis after 30 evaluable patients and a maximum enrolment of 60 patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer (Advanced/Metastatic)
What is being tested?
SRS/fSRT+T-Dxd
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
No sites listed yet
Study dates
15 May 2027to 31 Dec 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Women or men aged ≥18 years at the time of informed consent.
  • Histologically or cytologically confirmed breast cancer with documented HER2-positive status, defined as immunohistochemistry (IHC) 3+ or IHC 2+ with in situ hybridization (ISH) amplification ratio ≥2.0 or average HER2 copy number ≥6.0 signals/cell, per ASCO/CAP guidelines [31]. HER2 status may be determined on primary tumour or metastatic biopsy.
  • Radiologically confirmed metastatic disease (Stage IV) with first diagnosis of BMs documented on contrast-enhanced magnetic resonance imaging (MRI) of the brain performed within 28 days prior to enrolment.
  • Brain metastases amenable to SRS/fSRT, defined as 1 to 10 intracranial lesions with a cumulative planned target volume (PTV) ≤20.0 mL. Individual lesion diameter must not exceed 30 mm in the longest axis.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 at screening.
  • Stable or decreasing corticosteroid dose equivalent to ≤4 mg/day dexamethasone for a minimum of 5 consecutive days prior to Day 1 of Cycle 1.
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  • Adequate organ function documented within 14 days prior to enrolment, defined as:
  • Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L
  • Platelet count ≥100 × 10⁹/L
  • Haemoglobin ≥9.0 g/dL (transfusion permitted if stable for ≥7 days)
  • Total bilirubin ≤1.5 × upper limit of normal (ULN); ≤3 × ULN if documented Gilbert syndrome Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN (≤5 × ULN if liver metastases present)
  • Estimated creatinine clearance ≥30 mL/min (Cockcroft-Gault formula)
  • Left ventricular ejection fraction (LVEF) ≥50% by echocardiography or multigated acquisition (MUGA) scan within 28 days of enrolment
  • Adequate pulmonary function defined as oxygen saturation ≥92% on room air at rest and no clinical or radiographic evidence of interstitial lung disease (ILD) or pneumonitis on baseline chest computed tomography (CT) performed within 28 days of enrolment.
  • For women of childbearing potential: negative serum pregnancy test within 7 days prior to Day 1 of Cycle 1 and agreement to use highly effective contraception (combined hormonal or intrauterine device or bilateral tubal occlusion or vasectomized partner or sexual abstinence) from screening through at least 7 months after the last dose of T-DXd. For men with female partners of childbearing potential: agreement to use barrier contraception from screening through at least 4 months after the last dose of T-DXd.
  • Ability to understand and willingness to sign a written informed consent document in accordance with ICH E6(R2) Good Clinical Practice guidelines and local regulatory requirements [16].
  • Willingness and ability to comply with scheduled visits, treatment plan, imaging assessments (see Section 8), and laboratory evaluations for the duration of the study.

Who cannot join

  • Prior treatment with T-DXd or any other HER2-directed antibody-drug conjugate employing a topoisomerase I inhibitor payload in the metastatic setting. Patients with metastatic disease who previously received T-DXd in the (neo)adjuvant setting are eligible, provided that at least 24 months have elapsed since the last T-DXd administration and that disease progression did not occur during T-DXd treatment.
  • Leptomeningeal carcinomatosis confirmed by cerebrospinal fluid cytology or unequivocal MRI findings (linear or nodular leptomeningeal enhancement with associated clinical symptoms).
  • Any prior radiation therapy to the brain.
  • Brain metastases requiring urgent neurosurgical intervention (e.g., lesions causing midline shift >5 mm, obstructive hydrocephalus, or impending herniation).
  • Significant cardiovascular disease, including:
  • LVEF <50% at screening History of New York Heart Association (NYHA) Class III or IV congestive heart failure
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  • Myocardial infarction within 6 months prior to enrolment
  • History of non-infectious ILD/pneumonitis requiring systemic corticosteroids, or current ILD/pneumonitis of any grade, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
  • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals at the time of enrolment.
  • Known active hepatitis B (HBsAg positive with detectable HBV DNA), active hepatitis C (detectable HCV RNA), or known HIV infection with CD4 count <200 cells/μL or detectable viral load.
  • Active autoimmune disease requiring systemic immunosuppressive therapy (>10 mg/day prednisone equivalent) within 14 days prior to enrolment. Replacement-dose corticosteroids (e.g., for adrenal insufficiency) and topical, inhaled, or ophthalmic corticosteroids are permitted.
  • Major surgical procedure within 28 days prior to enrolment or anticipated need for major surgery during the study treatment period.
  • Concurrent malignancy requiring active systemic treatment, with the exception of adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or other malignancies in complete remission for ≥3 years.
  • Known hypersensitivity to T-DXd, other antibody-drug conjugates, or any excipient of the investigational product formulation (L-histidine, L-histidine hydrochloride monohydrate, sucrose, polysorbate 80).
  • Pregnancy, lactation, or intention to become pregnant during the study or within 7 months after the last dose of T-DXd.
  • Any condition that, in the investigator's judgment, would compromise the patient's ability to comply with study procedures, confound interpretation of study results, or pose unacceptable risk to the patient.
  • Concurrent participation in another interventional clinical trial with an investigational medicinal product. Participation in observational studies or registries is permitted.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Luca Visani, MD contact

+390557947848

luca.visani@unifi.it

About this study

Official title: A Phase II, Single-Arm, Bayesian Adaptive Study of Trastuzumab Deruxtecan in Combination With Stereotactic Radiosurgery in Patients With HER2-Positive Metastatic Breast Cancer and First Diagnosis of Brain Metastases (HERBRAIN)

This is a Phase II, single-arm, Bayesian adaptive trial. The study employs a two-stage design with an interim analysis after 30 evaluable patients and a maximum enrolment of 60 patients. T-DXd is administered at 5.4 mg/kg intravenously every 3 weeks until intracranial or systemic progression, unacceptable toxicity, or patient withdrawal. SRS (single-fraction) or fractionated stereotactic radiotherapy (fSRT, 3-5 fractions) is delivered within 21 days of enrolment, before Cycle 1 (with a minimum interval of 10 days from local treatment completion and Cycle 1 of T-DXd and a maximum interval of 28 days), for patients with 1-10 BMs and cumulative planning target volume ≤ 20.0 mL.

Being tested
SRS/fSRT+T-Dxd
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

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

  • SRS/fSRT+T-DxdDrug

    Patients will be trated with SRS/fSRT followed by Trastuzumab deruxtecan (T-DXd) 5.4 mg/kg administered as an intravenous infusion every 21 days (q3w).

Study groups in NCT07905313
Study groupRoleWhat they receive
AExperimentalNot described
Receives: Drug: SRS/fSRT+T-Dxd

What is being measured

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

  1. 12-month CNS-PFS rate

    Measured: From enrollment to End of Treatment, up to 30 months

Timeline

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

  1. First posted29 Oct 2026
  2. Study start15 May 2027 (estimated)
  3. Primary completion15 May 2028 (estimated)
  4. Study completion31 Dec 2030 (estimated)

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
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07905313
Sponsor's protocol ID
HERBRAIN
Acronym
HERBRAIN
Status last verified
Oct 2026
First submitted
22 Oct 2026
Last updated
29 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: IPD will be maintained in a local data repository

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SRS/fSRT+T-Dxd in people with Breast Cancer (Advanced/Metastatic), run by Azienda Ospedaliero-Universitaria Careggi.

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 17 inclusion and 17 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: opening soon, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

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?

This study is still under way. Results are not available in the source record yet.

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

Contact Luca Visani, MD (+390557947848, luca.visani@unifi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

12-month CNS-PFS rate (time frame: From enrollment to End of Treatment, up to 30 months). 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 NCT07905313.

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 29 Oct 2026.

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