Premedication With Dexamethasone for Preventing Interstitial Lung Disease in Patients With Breast Cancer Treated With Trastuzumab Deruxtecan (MARGARET)

September 14, 2026 updated by: Mario Negri Institute for Pharmacological Research

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 in 10-15% of patients. 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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
244

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Provision of signed, written and dated study informed consent, data protection informed consent and any locally required
  2. 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.
  3. Histologically or cytologically confirmed metastatic breast cancer for which T-DXd treatment is approved and available at the participating center.

  4. Diagnosis of metastatic breast cancer candidate to start a treatment with T-DXd in the subsequent settings:

    1. HR-positive with expression of HER2 (low or ultralow) ≤ 2 lines of chemotherapy in advanced disease
    2. HR-negative with expression of HER2-low ≤ 2 lines of chemotherapy in advanced disease
    3. HER2-positive independently from HR-positivity ≤ 3 lines of treatment in advanced disease
  5. ECOG performance status of 0 or 1.

  6. Adequate bone marrow as defined by the following laboratory values:

    1. ANC ≥1.5 × 109 /L
    2. Platelets ≥100 × 109 /L
    3. Hemoglobin ≥9.0 g/dL
  7. 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.
  8. Adequate washout before randomization, including ≥4 weeks from major surgery or chest radiotherapy (≥2 weeks for non-chest stereotactic radiotherapy)
  9. 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.

Exclusion Criteria:

  1. Patients with uncontrolled diabetes mellitus both type 1 and type 2 (HbA1c > 8.5%).
  2. Patients with contraindications to dexamethasone, as determined by the investigator in consultation with medical monitoring before enrolment.
  3. Patients already undergoing chronic steroid treatment (e.g. 10 mg/day of prednisone/prednisolone or equivalent).
  4. Patients requiring oxygen therapy at rest.
  5. Documented pneumonitis/ILD prior to Cycle 1 Day 1.
  6. 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.
  7. Impaired renal function with creatinine clearance <30 mL/min (calculated by Cockcroft-Gault formula).
  8. Active or newly diagnosed CNS metastases, including meningeal carcinomatosis.
  9. Patients with recent (<28 days) respiratory infections.
  10. 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.
  11. Palliative limited-field radiotherapy: <2 weeks (non-chest) or <4 weeks (chest or >30% bone marrow).
  12. 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.
  13. Active and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
  14. Evidence of ongoing alcohol or drug abuse as assessed by the Investigator.
  15. Any severe medical or psychiatric condition that, in the Investigator's opinion, would preclude the patient's participation in a clinical study
  16. 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.
  17. Known allergy or hypersensitivity to study drugs or any excipient.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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. 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.
Drug: Dexamethasone
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.
Drug: antiemetic premedication
three-drug combination-5-HT3 receptor antagonists, NK1 receptor antagonists, and dexamethasone
Drug: T-DXd
T-DXd treatment in patients with metastatic breast cancer
Active Comparator: Arm B (control arm)
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.
Drug: antiemetic premedication
three-drug combination-5-HT3 receptor antagonists, NK1 receptor antagonists, and dexamethasone
Drug: T-DXd
T-DXd treatment in patients with metastatic breast cancer

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Primary endpoint
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.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mario Negri Institute for Pharmacological Research

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 20, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 20, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 20, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 14, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 18, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 18, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2025-521798-15-00 (Ctis)
  • 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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