Breast CancerPhase 3MARGARETNCT07828054
Premedication With Dexamethasone for Preventing Interstitial Lung Disease in Patients With Breast Cancer Treated With Trastuzumab Deruxtecan
A Phase 3 study testing Dexamethasone, antiemetic premedication and T-DXd in people with Breast Cancer and Interstitial Lung Disease (ILD), run by Mario Negri Institute for Pharmacological Research.
Trial summary
Trastuzumab deruxtecan (T-DXd) has recently received approval as an antibody-drug conjugate for treating patients with metastatic breast cancer (BC) who have HER-2 protein expression as determined by immunohistochemistry, including HER2-positive, -low and -ultralow BC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Interstitial Lung Disease (ILD)
- What is being tested?
- Dexamethasone, antiemetic premedication and T-DXd
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 244 participants
- Where
- No sites listed yet
- Study dates
- 20 Dec 2026to 20 Dec 2030
- Phase
- Phase 3
- 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
- Provision of signed, written and dated study informed consent, data protection informed consent and any locally required
- Women or men aged ≥18 years (or the minimum age of consent in accordance with the local law), at the time of informed consent signature.
- Histologically or cytologically confirmed metastatic breast cancer for which T-DXd treatment is approved and available at the participating center.
- Diagnosis of metastatic breast cancer candidate to start a treatment with T-DXd in the subsequent settings:
- HR-positive with expression of HER2 (low or ultralow) ≤ 2 lines of chemotherapy in advanced disease
- HR-negative with expression of HER2-low ≤ 2 lines of chemotherapy in advanced disease
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- HER2-positive independently from HR-positivity ≤ 3 lines of treatment in advanced disease
- ECOG performance status of 0 or 1.
- Adequate bone marrow as defined by the following laboratory values:
- ANC ≥1.5 × 109 /L
- Platelets ≥100 × 109 /L
- Hemoglobin ≥9.0 g/dL
- Adequate hepatic function: Serum albumin ≥ 2.5 g/dL; total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 3 in patients with liver metastases or know history of Gilbert's disease); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times ULN (≤ 5 in patients with liver metastases); international normalized ratio (INR) < 1.5.
- Adequate washout before randomization, including ≥4 weeks from major surgery or chest radiotherapy (≥2 weeks for non-chest stereotactic radiotherapy)
- Patient willing and able to comply with the protocol procedures for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.
Who cannot join
- Patients with uncontrolled diabetes mellitus both type 1 and type 2 (HbA1c > 8.5%).
- Patients with contraindications to dexamethasone, as determined by the investigator in consultation with medical monitoring before enrolment.
- Patients already undergoing chronic steroid treatment (e.g. 10 mg/day of prednisone/prednisolone or equivalent).
- Patients requiring oxygen therapy at rest.
- Documented pneumonitis/ILD prior to Cycle 1 Day 1.
- Uncontrolled or significant cardiovascular disease, including recent myocardial infarction (within 6 months), symptomatic heart failure (NYHA II-IV), elevated troponin without symptoms requiring cardiology evaluation, uncontrolled hypertension or arrhythmias, and QTcF prolongation >470 ms in females or >450 ms in males.
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- Impaired renal function with creatinine clearance <30 mL/min (calculated by Cockcroft-Gault formula).
- Active or newly diagnosed CNS metastases, including meningeal carcinomatosis.
- Patients with recent (<28 days) respiratory infections.
- Inability to take oral medications, refractory or chronic nausea, gastrointestinal conditions (including significant gastric or bowel resection), history of malabsorption syndrome, or any other uncontrolled gastrointestinal condition that impacts the absorption of the study drug.
- Palliative limited-field radiotherapy: <2 weeks (non-chest) or <4 weeks (chest or >30% bone marrow).
- Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 390 days after the last dose of IMP.
- Active and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
- Evidence of ongoing alcohol or drug abuse as assessed by the Investigator.
- Any severe medical or psychiatric condition that, in the Investigator's opinion, would preclude the patient's participation in a clinical study
- Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during study participation. Female subjects without childbearing potential are defined as women who are surgically sterile (hysterectomy or documented bilateral tubal ligation) or postmenopausal, defined as at least 12 months of spontaneous amenorrhea.
- Known allergy or hypersensitivity to study drugs or any excipient.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Premedication With Dexamethasone for Preventing Interstitial Lung Disease in Patients With Breast Cancer Treated With Trastuzumab Deruxtecan - MARGARET Trial
Trastuzumab deruxtecan (T-DXd) has recently received approval as an antibody-drug conjugate for treating patients with metastatic breast cancer (BC) who have HER-2 protein expression as determined by immunohistochemistry, including HER2-positive, -low and -ultralow BC. Its use has shown significant effectiveness in terms of response and survival rates. Pulmonary toxicity, specifically interstitial lung disease (ILD), is of significant clinical interest. For cases of mild toxicity, namely grade 1, the diagnosis relies exclusively on radiological findings in the absence of symptoms. In such cases, T-DXd is temporarily stopped and steroids might be used as treatment. Once the radiological findings have been resolved, the drug can be resumed. Grade 2 is distinguished by the presence of clinical signs such as difficulty breathing and coughing, as well as radiological evidence. In such instances, the medication must be permanently stopped. As a consequence, it is recommended that patients receiving T-DXd treatment should be closely monitored with high-resolution (HR) CT scans every 6-12 weeks. The precise mechanism responsible for this toxicity has not yet been fully elucidated; but it is thought to be inflammatory in origin The risk factors for ILD include lower baseline SpO2, lung comorbidities, reduced renal function, time from initial diagnosis, and drug dose. Administering dexamethasone as a premedication twice a day from the day before T-DXd infusion (D-1) through day 4 (D4) may lower ILD incidence and help prevent permanent T-DXd treatment discontinuation. Primary objective To assess the efficacy of dexamethasone premedication in reducing the occurrence of ILD >G1 in breast cancer patients receiving T-DXd treatment.
- Conditions
- Breast Cancer, Interstitial Lung Disease (ILD)
- Being tested
- Dexamethasone, antiemetic premedication, T-DXd
- Keywords
- breast cancer, interstitial lung disease (ILD), dexamethasone, premedication
- Medical subject headings
- Breast Neoplasms, Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Arm A (experimental arm): patients will receive premedication with dexamethasone 4 mg twice a day from D-1 to D4, in addition to recommended standard antiemetic premedication.
antiemetic premedicationDrug
three-drug combination-5-HT3 receptor antagonists, NK1 receptor antagonists, and dexamethasone
T-DXdDrug
T-DXd treatment in patients with metastatic breast cancer
| Study group | Role | What they receive |
|---|---|---|
| Arm A (experimental arm) - Dexamethasone+standard antiemetic premedication+T-DXd infusion | Experimental | patients will receive premedication with dexamethasone 4 mg twice a day from D-1 to D4, in addition to recommended standard antiemetic premedication. For both arms, the recommended standard antiemetic premedication consists of a three-drug combination-5-HT3 receptor antagonists, NK1 receptor antagonists, and dexamethasone-administered on the first day of T-DXd infusion. Receives: Drug: Dexamethasone; Drug: antiemetic premedication; Drug: T-DXd |
| Arm B (control arm) - Standard antiemetic premedication+T-DXd infusion | Active comparator | patients will receive recommended standard antiemetic premedication. For both arms, the recommended standard antiemetic premedication consists of a three-drug combination-5-HT3 receptor antagonists, NK1 receptor antagonists, and dexamethasone-administered on the first day of T-DXd infusion. Receives: Drug: antiemetic premedication; Drug: T-DXd |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint - Cumulative incidence, patients who experience an ILD > G1
Cumulative incidence of patients who experience an ILD > G1 on high-resolution thorax CT scan during the treatment with T-DXd at 12 months from randomization by local Investigator's judgement according to CTCAE, version 6.0. Discontinuation of T-DXd treatment for any reason other than ILD >G1 will be considered as a competing event.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2026
- Study start20 Dec 2026 (estimated)
- Primary completion20 Dec 2030 (estimated)
- Study completion20 Dec 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.
- More trials run by Mario Negri Institute for Pharmacological ResearchThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 244 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07828054
- Sponsor's protocol ID
- 2025-521798-15-00
- Other IDs
- 2025-521798-15-00, 2025
- Acronym
- MARGARET
- Status last verified
- Oct 2026
- First submitted
- 14 Sep 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan no share
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Premedication With Dexamethasone for Preventing Interstitial Lung Disease in Patients With Breast Cancer Treated With Trastuzumab Deruxtecan - MARGARET Trial
- ClinicalTrials.gov ID
- NCT07828054
- Acronym / sponsor ID
- MARGARET / 2025-521798-15-00
- Conditions
- Breast Cancer, Interstitial Lung Disease (ILD)
- Keywords
- breast cancer, interstitial lung disease (ILD), dexamethasone, premedication
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 244 participants (estimated)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- 20 Dec 2026 (estimated)
- Primary completion
- 20 Dec 2030 (estimated)
- Study completion
- 20 Dec 2030 (estimated)
- First posted
- 18 Sep 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.
Trastuzumab deruxtecan (T-DXd) has recently received approval as an antibody-drug conjugate for treating patients with metastatic breast cancer (BC) who have HER-2 protein expression as determined by immunohistochemistry, including HER2-positive, -low and -ultralow BC. Its use has shown significant effectiveness in terms of response and survival rates. Pulmonary toxicity, specifically interstitial lung disease (ILD), is of significant clinical interest. For cases of mild toxicity, namely grade 1, the diagnosis relies exclusively on radiological findings in the absence of symptoms. In such cases, T-DXd is temporarily stopped and steroids might be used as treatment. Once the radiological findings have been resolved, the drug can be resumed. Grade 2 is distinguished by the presence of clinical signs such as difficulty breathing and coughing, as well as radiological evidence. In such instances, the medication must be permanently stopped. As a consequence, it is recommended that patients receiving T-DXd treatment should be closely monitored with high-resolution (HR) CT scans every 6-12 weeks. The precise mechanism responsible for this toxicity has not yet been fully elucidated; but it is thought to be inflammatory in origin The risk factors for ILD include lower baseline SpO2, lung comorbidities, reduced renal function, time from initial diagnosis, and drug dose. Administering dexamethasone as a premedication twice a day from the day before T-DXd infusion (D-1) through day 4 (D4) may lower ILD incidence and help prevent permanent T-DXd treatment discontinuation. Primary objective To assess the efficacy of dexamethasone premedication in reducing the occurrence of ILD >G1 in breast cancer patients receiving T-DXd treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (experimental arm) - Dexamethasone+standard antiemetic premedication+T-DXd infusion | Experimental | Drug: Dexamethasone, Drug: antiemetic premedication, Drug: T-DXdpatients will receive premedication with dexamethasone 4 mg twice a day from D-1 to D4, in addition to recommended standard antiemetic premedication. For both arms, the recommended standard antiemetic premedication consists of a three-drug combination-5-HT3 receptor antagonists, NK1 receptor antagonists, and dexamethasone-administered on the first day of T-DXd infusion. |
| Arm B (control arm) - Standard antiemetic premedication+T-DXd infusion | Active comparator | Drug: antiemetic premedication, Drug: T-DXdpatients will receive recommended standard antiemetic premedication. For both arms, the recommended standard antiemetic premedication consists of a three-drug combination-5-HT3 receptor antagonists, NK1 receptor antagonists, and dexamethasone-administered on the first day of T-DXd infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Provision of signed, written and dated study informed consent, data protection informed consent and any locally required
- Women or men aged ≥18 years (or the minimum age of consent in accordance with the local law), at the time of informed consent signature.
- Histologically or cytologically confirmed metastatic breast cancer for which T-DXd treatment is approved and available at the participating center.
- Diagnosis of metastatic breast cancer candidate to start a treatment with T-DXd in the subsequent settings:
- ECOG performance status of 0 or 1.
Key exclusion criteria (17 listed)
- Patients with uncontrolled diabetes mellitus both type 1 and type 2 (HbA1c > 8.5%).
- Patients with contraindications to dexamethasone, as determined by the investigator in consultation with medical monitoring before enrolment.
- Patients already undergoing chronic steroid treatment (e.g. 10 mg/day of prednisone/prednisolone or equivalent).
- Patients requiring oxygen therapy at rest.
- Documented pneumonitis/ILD prior to Cycle 1 Day 1.
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 |
|---|---|---|
| DexamethasoneArm A (experimental arm): patients will receive premedication with dexamethasone 4 mg twice a day from D-1 to D4, in addition to recommended standard antiemetic premedication. | Drug | Arm A (experimental arm) - Dexamethasone+standard antiemetic premedication+T-DXd infusion |
| antiemetic premedicationthree-drug combination-5-HT3 receptor antagonists, NK1 receptor antagonists, and dexamethasone | Drug | Arm A (experimental arm) - Dexamethasone+standard antiemetic premedication+T-DXd infusion, Arm B (control arm) - Standard antiemetic premedication+T-DXd infusion |
| T-DXdT-DXd treatment in patients with metastatic breast cancer | Drug | Arm A (experimental arm) - Dexamethasone+standard antiemetic premedication+T-DXd infusion, Arm B (control arm) - Standard antiemetic premedication+T-DXd infusion |
Primary outcome
Primary endpoint - Cumulative incidence, patients who experience an ILD > G1
Time frame: 12 months
Cumulative incidence of patients who experience an ILD > G1 on high-resolution thorax CT scan during the treatment with T-DXd at 12 months from randomization by local Investigator's judgement according to CTCAE, version 6.0. Discontinuation of T-DXd treatment for any reason other than ILD >G1 will be considered as a competing event.
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 19 Oct 2026.
- Individual participant dataSharing planned: No. No plan no share
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexamethasone, antiemetic premedication and T-DXd in people with Breast Cancer and Interstitial Lung Disease (ILD), run by Mario Negri Institute for Pharmacological Research.
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 15 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 19 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Irene De Simone, MSc (+39 ext. 0239014661, irene.desimone@marionegri.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary endpoint - Cumulative incidence, patients who experience an ILD > G1 (time frame: 12 months). 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 19 Oct 2026.