Breast CancerPhase 1NCT07454668
Trastuzumab Deruxtecan + Stereotactic Radiosurgery (SRS) in HER2+ Breast Cancer Brain Metastases
A Phase 1 study testing Trastuzumab Deruxtecan and Stereotactic Radiosurgery in people with Breast Cancer and HER2-positive Breast Cancer, run by Baptist Health South Florida at 1 site in United States.
Trial summary
A phase I clinical trial (a type of research study) for people with human epidermal growth factor receptor 2 (HER-2) positive breast cancer with metastasis to the brain. This research study will evaluate how well brain metastases can be controlled using a type of radiation therapy known as stereotactic radiosurgery… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, HER2-positive Breast Cancer, Brain Metastases
- What is being tested?
- Trastuzumab Deruxtecan and Stereotactic Radiosurgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2027to Feb 2030
- Phase
- Phase 1
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed HER-2-positive breast cancer with newly diagnosed brain metastases.
- ECOG Performance Status (PS) of 0, 1, 2.
- Participants with 1-10 brain metastases will be candidates for T-DXd with SRS at the discretion of the treating radiation oncologist. Intra-cranial metastasis must measure 3 cm or less in the greatest dimension.
- Age ≥ 18 years
- Signed written informed consent by patient or legally authorized representative. A signed informed consent must be obtained prior to any study-specific procedures.
- Life expectancy of at least 12 weeks.
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- Any number of prior systemic therapies will be allowed, except T-DXd.
- Hemoglobin ≥ 9 g/dL, White blood count ≥ 3.0 × 109/L, Absolute Neutrophil count ≥ 1.5 × 109/L and platelet count ≥ 100 × 109/L.
- Serum bilirubin ≤ 1.5 × upper limit of normal (ULN).
- AST and/or ALT ≤ 2 × ULN (≤ 5 × ULN when clearly attributable to the presence of liver metastases).
- Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance > 60 mL/min.
- Ability to comply with study procedures and monitoring.
- For individuals of childbearing potential, a negative pregnancy test should be obtained within 7 days prior to the start of therapy.
- Participants must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within 28 days before enrollment (to be assessed as clinically indicated).
- Male or female participants of reproductive potential need to employ two highly effective and acceptable forms of contraception throughout their participation in the study and for 7 months after last dose of T-DXd.
- Highly effective and acceptable forms of contraception are:
- Male condom plus spermicide
- Cap plus spermicide
- Diaphragm plus spermicide
- Copper T
- Progesterone T
- Levonorgestrel-releasing intrauterine system (e.g., Mirena®)
- Implants
- Hormone shot or injection
- Combined pill
- Mini-pill
- Patch
- Postmenopausal individuals on the study (that will not need contraception) is defined as:
- Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments.
- LH and FSH levels in the postmenopausal range for individuals < 50 years.
- Radiation-induced oophorectomy with last menses > 1 year ago.
- Chemotherapy-induced menopause with > 1 year interval since last menses.
- Surgical sterilization (bilateral oophorectomy or hysterectomy).
- Men and women and members of all races and ethnic groups are eligible for this trial.
Who cannot join
- Participants with leptomeningeal metastases documented by MRI or CSF evaluation.
- Evidence of intra-tumoral or peri-tumoral hemorrhage deemed clinically significant by the treating physician.
- Brain metastases within 5 mm of the optic chiasm or optic nerve.
- Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom, e.g., Crohn's disease, malabsorption, or CTCAE grade > 2 diarrhea of any etiology at baseline.
- History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, New York Heart Association (NYHA) functional classification of 3 or 4.
- Unable to undergo brain MRI.
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- Screen for human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C. HIV/HBV/HCV testing per institutional practice.
- All toxicities from prior therapies must have resolved to CTCAE v5.0 grade 1 or better by the time of study enrollment.
- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active, or uncontrolled infection, uncontrolled diabetes, second active malignancy) that could cause unacceptable safety risks or compromise compliance with the protocol.
- Currently receiving other investigational cancer therapy (with the exception of continuing therapy with GnRH analogues) within 4 weeks prior to start of study treatment.
- Mean QT interval corrected heart rate (QTc) ≥ 470 ms calculated from 3 electrocardiograms using Fredericia's Correction, calculated as: 8.22 ∛(RR interval)
- LVEF <50%.
- Ineligible for treatment with T-DXd.
- Ineligible for treatment with SRS.
- Active or prior documented ILD/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- History of hypersensitivity to T-DXd.
- History and/or confirmed corneal ulceration.
- Pregnant or breast feeding. The patients should not breast feed for 7 months after stopping the drug.
- Use of anthracyclines will be prohibited while on the protocol.
- Prior cranial radiation is not allowed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Baptist Health Herbert Wertheim Cancer Institute
Miami, Florida, 33176
Manmeet Ahluwalia, MD, 786-596-2000, ManmeetA@baptisthealth.net
Multisite Research Program, 786-596-2000, MCIMultisiteResearch@baptisthealth.net
About this study
Official title: Phase 1 Trial of Trastuzumab Deruxtecan With Stereotactic Radiosurgery (SRS) in Participants With Brain Metastases From HER-2 Positive Breast Cancer
A phase I clinical trial (a type of research study) for people with human epidermal growth factor receptor 2 (HER-2) positive breast cancer with metastasis to the brain. This research study will evaluate how well brain metastases can be controlled using a type of radiation therapy known as stereotactic radiosurgery (SRS) when combined with the therapeutic agent Trastuzumab Deruxtecan (T-DXd). The combined use of SRS with T-DXd is considered investigational.
- Being tested
- Trastuzumab Deruxtecan, Stereotactic Radiosurgery
- Medical subject headings
- Breast Neoplasms, Brain Neoplasms, Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab DeruxtecanDrug
Also called T-DXd
T-DXd will be given as an IV infusion every 21 days. This Phase 1 study will use predefined dose levels (5.4 mg/kg, 4.4 mg/kg, and 3.2 mg/kg) to evaluate safety and tolerability. Participants may continue treatment until disease progression, unacceptable side effects, or withdrawal.
Stereotactic RadiosurgeryRadiation
Also called SRS
Participants will receive SRS to intact brain metastases. Typical dosing is 20-24 Gy in a single fraction for lesions <20 mm, or 27 Gy in 3 fractions for lesions ≥20 mm. Exact dosing will be based on the treating radiation oncologist's clinical judgment.
| Study group | Role | What they receive |
|---|---|---|
| T-DXd + SRS | Experimental | All participants will receive SRS and the drug T-DXd. The goal is to evaluate safety and determine an appropriate dose. Receives: Drug: Trastuzumab Deruxtecan; Radiation: Stereotactic Radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs)
DLTs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 starting from the first dose of T-DXd through 3 weeks after SRS. DLT is defined as the appearance of side effects during treatment that are severe enough to prevent continuation of treatment at a participant's assigned dose. Any of the following events will be considered a DLT if treatment-related:
- ≥ Grade 4 non-hematologic toxicity except nausea and vomiting (if manageable with supportive care measures), alopecia, drug-related fever, and toxicities secondary to neutropenia and sepsis
- ≥ Grade 3 neurologic toxicity (sensory or autonomic)
- Grade 4 platelet count (<25,000/mm³) 50 days beyond the start of the most recent chemotherapy (not related to recurrent leukemia)
- Grade 4 neutropenia 50 days beyond the start of the most recent chemotherapy (not related to recurrent leukemia)
- Grade 3 non-hematologic toxicity (excluding alopecia or toxicities secondary to neutropenia
Measured: 3 weeks
Determination of the maximum tolerated dose (MTD) of T-DXd in combination with SRS
The MTD will be determined using a standard 3+3 dose de-escalation design across predefined dose levels of T-DXd (5.4 mg/kg, 4.4 mg/kg, and 3.2 mg/kg IV every 21 days), based on the number of participants who experience a DLT at each dose level.
Measured: 3 weeks
Secondary outcomes (8)
Intracranial Progression-free survival (PFS) at 6 months (PFS-6)
Intracranial PFS-6 will be defined as the time from first dose of study drug until intracranial disease progression (i.e., progression within the skull) or death from any cause using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at 6 months post-treatment. Progression is defined as at least 20% increase in the sum of the longest diameters of the target lesions, appearance of any new lesions, or unequivocable progression of any non-target lesions. For participants whose disease has not progressed at the time of the analysis, censoring will be performed using the date of the last valid disease assessment.
Measured: 6 months
Extracranial PFS-6
Extracranial PFS-6 will be defined as the time from first dose of study drug until extracranial disease progression (i.e., progression outside of the skull) or death from any cause using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at 6 months post-treatment. Progression is defined as at least 20% increase in the sum of the longest diameters (LD) of the target lesions compared to the smallest recorded LD since treatment started, appearance of any new lesions, or unequivocable progression of any non-target lesions. For participants whose disease has not progressed at the time of the analysis, censoring will be performed using the date of the last valid disease assessment.
Measured: 6 months
Overall survival (OS)
Median OS will be defined as the time from the beginning of study drug treatment until death due to any cause at the end of the study (~2 years). For participants who have not died at the time of the analysis, censoring will be performed using the date the participant was last known to be alive.
Measured: 2 years
Objective response rate (ORR)
ORR will be defined as the proportion of participants achieving a complete response (CR) or partial response (PR) using RECIST v1.1 as their best overall response by the end of the study (~2 years). Participants with CR or PR will be counted as successes and all other participants (including those with missing response information) will be counted as failures. CR is defined as disappearance of all target and non-target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions. All lymph nodes must be non-pathological in size (<10 mm short axis). PR is defined as at least 30% decrease in the sum of the LD of target lesions compared to baseline. There can be no appearance of new lesions.
Measured: 2 years
Intracranial PFS-6 comparison to historical data
Intracranial PFS-6 as defined in Outcome 3 will be compared to historical data.
Measured: 6 months
Extracranial PFS-6 comparison to historical data
Extracranial PFS-6 as defined in Outcome 4 will be compared to historical data.
Measured: 6 months
OS comparison to historical data
Median OS as defined in Outcome 5 will be compared to historical data.
Measured: 2 years
ORR comparison to historical data
ORR as defined in Outcome 6 will be compared to historical data.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2026
- Study startJan 2027 (estimated)
- Primary completionFeb 2029 (estimated)
- Study completionFeb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Model description
- This is a phase 1 multi-site, open-label, single-arm dose de-escalation study in participants with HER-2 positive breast cancer with 1-10 brain metastases.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baptist Health South Florida
- Sponsor type
- University, hospital or other
- Collaborators
- National Brain Tumor Society
- Responsible party
- Sponsor
- Investigators
- Manmeet Ahluwalia, Principal investigator, Baptist Health Herbert Wertheim Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07454668
- Sponsor's protocol ID
- 2025-AHL-001
- Status last verified
- Sep 2026
- First submitted
- 16 Feb 2026
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Trial of Trastuzumab Deruxtecan With Stereotactic Radiosurgery (SRS) in Participants With Brain Metastases From HER-2 Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT07454668
- Acronym / sponsor ID
- 2025-AHL-001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Baptist Health South FloridaUniversity, hospital or other
- Collaborators
- National Brain Tumor Society
- Study start
- Jan 2027 (estimated)
- Primary completion
- Feb 2029 (estimated)
- Study completion
- Feb 2030 (estimated)
- First posted
- 6 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A phase I clinical trial (a type of research study) for people with human epidermal growth factor receptor 2 (HER-2) positive breast cancer with metastasis to the brain. This research study will evaluate how well brain metastases can be controlled using a type of radiation therapy known as stereotactic radiosurgery (SRS) when combined with the therapeutic agent Trastuzumab Deruxtecan (T-DXd). The combined use of SRS with T-DXd is considered investigational.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a phase 1 multi-site, open-label, single-arm dose de-escalation study in participants with HER-2 positive breast cancer with 1-10 brain metastases.
| Arm | Type | Receives |
|---|---|---|
| T-DXd + SRS | Experimental | Drug: Trastuzumab Deruxtecan, Radiation: Stereotactic RadiosurgeryAll participants will receive SRS and the drug T-DXd. The goal is to evaluate safety and determine an appropriate dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- Histologically confirmed HER-2-positive breast cancer with newly diagnosed brain metastases.
- ECOG Performance Status (PS) of 0, 1, 2.
- Participants with 1-10 brain metastases will be candidates for T-DXd with SRS at the discretion of the treating radiation oncologist. Intra-cranial metastasis must measure 3 cm or less in the greatest dimension.
- Age ≥ 18 years
- Signed written informed consent by patient or legally authorized representative. A signed informed consent must be obtained prior to any study-specific procedures.
Key exclusion criteria (20 listed)
- Participants with leptomeningeal metastases documented by MRI or CSF evaluation.
- Evidence of intra-tumoral or peri-tumoral hemorrhage deemed clinically significant by the treating physician.
- Brain metastases within 5 mm of the optic chiasm or optic nerve.
- Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom, e.g., Crohn's disease, malabsorption, or CTCAE grade > 2 diarrhea of any etiology at baseline.
- History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, New York Heart Association (NYHA) functional classification of 3 or 4.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trastuzumab DeruxtecanAlso: T-DXdT-DXd will be given as an IV infusion every 21 days. This Phase 1 study will use predefined dose levels (5.4 mg/kg, 4.4 mg/kg, and 3.2 mg/kg) to evaluate safety and tolerability. Participants may continue treatment until disease progression, unacceptable side effects, or withdrawal. | Drug | T-DXd + SRS |
| Stereotactic RadiosurgeryAlso: SRSParticipants will receive SRS to intact brain metastases. Typical dosing is 20-24 Gy in a single fraction for lesions <20 mm, or 27 Gy in 3 fractions for lesions ≥20 mm. Exact dosing will be based on the treating radiation oncologist's clinical judgment. | Radiation | T-DXd + SRS |
Primary outcome
Incidence of dose-limiting toxicities (DLTs)
Time frame: 3 weeks
DLTs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 starting from the first dose of T-DXd through 3 weeks after SRS. DLT is defined as the appearance of side effects during treatment that are severe enough to prevent continuation of treatment at a participant's assigned dose. Any of the following events will be considered a DLT if treatment-related: * ≥ Grade 4 non-hematologic toxicity except nausea and vomiting (if manageable with supportive care measures), alopecia, drug-related fever, and toxicities secondary to neutropenia and sepsis * ≥ Grade 3 neurologic toxicity (sensory or autonomic) * Grade 4 platelet count (<25,000/mm³) 50 days beyond the start of the most recent chemotherapy (not related to recurrent leukemia) * Grade 4 neutropenia 50 days beyond the start of the most recent chemotherapy (not related to recurrent leukemia) * Grade 3 non-hematologic toxicity (excluding alopecia or toxicities secondary to neutropenia
Determination of the maximum tolerated dose (MTD) of T-DXd in combination with SRS
Time frame: 3 weeks
The MTD will be determined using a standard 3+3 dose de-escalation design across predefined dose levels of T-DXd (5.4 mg/kg, 4.4 mg/kg, and 3.2 mg/kg IV every 21 days), based on the number of participants who experience a DLT at each dose level.
8 secondary outcomes
Intracranial Progression-free survival (PFS) at 6 months (PFS-6)
Time frame: 6 months
Extracranial PFS-6
Time frame: 6 months
Overall survival (OS)
Time frame: 2 years
Objective response rate (ORR)
Time frame: 2 years
Intracranial PFS-6 comparison to historical data
Time frame: 6 months
Extracranial PFS-6 comparison to historical data
Time frame: 6 months
OS comparison to historical data
Time frame: 2 years
ORR comparison to historical data
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
- Baptist Health Herbert Wertheim Cancer InstituteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Manmeet Ahluwalia principal investigator
Baptist Health Herbert Wertheim Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Trastuzumab Deruxtecan and Stereotactic Radiosurgery in people with Breast Cancer and HER2-positive Breast Cancer, run by Baptist Health South Florida 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 34 inclusion and 20 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 1 Oct 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 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?
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 Manmeet Ahluwalia, M.D. (786-596-2000, ManmeetA@baptisthealth.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (DLTs) (time frame: 3 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Oct 2026.