Trastuzumab Deruxtecan Versus Standard Neoadjuvant Treatment for HER2-positive Breast Cancer
NCT ID: NCT05900206
Last Updated: 2025-09-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
370 participants
INTERVENTIONAL
2023-10-26
2032-04-30
Brief Summary
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* is T-DXd more effective than standard preoperative treatment?
* are there markers in the tumor or blood of patients with HER2-positive breast cancer that can help us predict response to treatment?
Participants will be divided into two groups, where one group will be treated with three courses of T-DXd and the other group will be treated with three courses standard of care treatment. Thereafter, further treatment will be decided by the tumor's molecular subtype.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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T-DXd (cycles 1-3)
Trastuzumab Deruxtecan, administered every three weeks for three courses. Further treatment is decided by the intrinsic molecular (PAM50) subtype of the tumor.
Trastuzumab deruxtecan
Experimental drug. Provided in 100mg vials. IV infusion.
Standard treatment (TCHP or PCHP; cycles 1-3)
TCHP (Docetaxel, Carboplatin, Trastuzumab, Pertuzumab) or PCHP (Paclitaxel, Carboplatin, Trastuzumab, Pertuzumab), administered every three weeks for three courses. Further treatment is decided by the intrinsic molecular (PAM50) subtype of the tumor.
Docetaxel
Active comparator. IV infusion.
Paclitaxel
Active comparator. IV infusion.
Carboplatin
Active comparator. IV infusion.
Trastuzumab
Active comparator. IV infusion.
Pertuzumab
Active comparator. IV infusion.
ER-positive and Luminal (cycles 4-6)
Ribociclib, letrozole, trastuzumab, pertuzumab
Ribociclib
Experimental drug. Tablets.
Letrozole
Experimental drug. Tablets.
ER-negative and Luminal, or Basal-like, or Normal-like (cycles 4-6)
Epirubicin and Cyclophosphamide in case of no complete radiologic response after the initial three courses. In case of complete radiologic response, treatment from cycles 1-3 (T-DXd or TCHP/PCHP) will continue instead for three more courses.
Epirubicin
Active comparator. IV infusion.
Cyclophosphamide
Active comparator. IV infusion.
HER2-enriched (cycles 4-6)
The same treatment with T-DXd or TCHP/PCHP administered every three weeks for three more courses will continue from cycles 1-3
Trastuzumab deruxtecan
Experimental drug. Provided in 100mg vials. IV infusion.
Docetaxel
Active comparator. IV infusion.
Paclitaxel
Active comparator. IV infusion.
Carboplatin
Active comparator. IV infusion.
Trastuzumab
Active comparator. IV infusion.
Pertuzumab
Active comparator. IV infusion.
Interventions
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Trastuzumab deruxtecan
Experimental drug. Provided in 100mg vials. IV infusion.
Docetaxel
Active comparator. IV infusion.
Paclitaxel
Active comparator. IV infusion.
Carboplatin
Active comparator. IV infusion.
Trastuzumab
Active comparator. IV infusion.
Pertuzumab
Active comparator. IV infusion.
Ribociclib
Experimental drug. Tablets.
Letrozole
Experimental drug. Tablets.
Epirubicin
Active comparator. IV infusion.
Cyclophosphamide
Active comparator. IV infusion.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations
3. Histologically confirmed breast cancer with an invasive component measuring ≥ 20 mm and/or with morphologically confirmed spread to regional lymph nodes (stage cT2-cT4 with any cN, or cN1-cN3 with any cT).
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the time of randomization (see Appendix B).
5. Known estrogen-receptor and/or progesterone receptor status, as assessed locally by IHC. The cut-off for positivity for ER/PR for this study is at least 10% of cell nuclei staining for ER or PR, respectively.
6. Known HER2-positive breast cancer defined as an IHC status of 3+. If IHC is 2+, a positive in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing. ISH positivity is defined as a ratio of ≥ 2 for the number of HER2 gene copies to the number of signals for chromosome 17 copies.
7. Left Ventricular Ejection Fraction (LVEF) ≥ 50%
8. Adequate bone-marrow, hepatic and renal function defined as laboratory tests within 7 days prior to enrolment:
i. Hematology:
1. Absolute granulocytes \> 1.5 x 109/L
2. Platelets \> 100 x 109/L
3. Hb \> 90 gr/L ii. Biochemistry
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1. Bilirubin ≤ upper limit of normal (ULN)
2. Serum creatinine ≤ 1.5 x ULN
3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 x ULN
4. Albumin ≥ 30 gr/L iii. Coagulation:
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1. INR/PT ≤ 1.5 x ULN, unless the subject is receiving anticoagulant therapy and INR/PT is within intended therapeutic range
2. aPTT ≤ 1.5 x ULN, unless the subject is receiving anticoagulant therapy and aPTT is within intended therapeutic range
9. Availability of tumor and blood samples as described in the protocol
10. Negative serum pregnancy test for women of childbearing potential or for patients who have experienced menopause onset \<12 months prior to randomization.
11. Patients of childbearing potential must be willing to use one highly effective contraception or two effective forms of nonhormonal contraception. See also 5.6 Precautions.
12. Participants must be able to communicate with the investigator and comply with the requirements of the study procedures
Exclusion Criteria
2. Presence of distant metastases, including node metastases in the contralateral thoracic region or in the mediastinum
3. Other malignancy diagnosed during the past five years, except adequately controlled limited basal cell carcinoma or squamous-cell carcinoma of the skin, in situ melanoma or carcinoma in situ of the cervix.
4. History of invasive breast cancer
5. History of DCIS, except for patients treated exclusively with mastectomy \>5 years prior to diagnosis of current breast cancer
6. Active cardiac disease or a history of cardiac dysfunction including any of the following:
1. History of unstable angina pectoris, myocardial infarction or recent (\<6 months) cardiovascular event including stroke and pericarditis
2. History of documented congestive heart failure (New York Heart Association functional classification II-IV)
3. Documented cardiomyopathy
4. QTc \> 450 msec as measured by Fridericia's formula, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
5. Uncontrolled hypertension
6. Symptomatic or uncontrolled arrhythmia, including atrial fibrillation.
7. Patients with ER-positive BC being treated with drugs recognized as strong inhibitors or inducers of the isoenzyme CYP3A (see table 5) which cannot be discontinued at least 7 days prior to planned treatment with ribociclib.
8. Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointes that cannot be discontinued or replaced by safe alternative medication
9. Pregnant or breastfeeding female patients, or patients who are planning to become pregnant
10. History of (non-infectious) Interstitial Lung Disease (ILD) / pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
11. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.)
12. Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.
13. Prior pneumonectomy
14. History of positive testing for HIV or known AIDS
15. Acute or chronic infection with hepatitis B or C virus
16. Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
17. Receipt of live, attenuated vaccine 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 30 days after the last dose of study drug.
18. Any psychological, including substance abuse, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
19. Allergic reactions or hypersensitivity to the study drugs or other monoclonal antibodies
20. Administration of other experimental drugs, either concomitantly or during the past 30 days before treatment initiation.
21. Pre-treatment axillary surgery
22. Recent major surgery (within 4 weeks from start of study treatment) or anticipated need for major surgery during the study.
23. A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
18 Years
ALL
No
Sponsors
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Karolinska University Hospital
OTHER
Responsible Party
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Theodoros Foukakis
Associate Professor
Principal Investigators
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Theodoros Foukakis, MD/PhD
Role: PRINCIPAL_INVESTIGATOR
Karolinska University Hospital
Alexios Matikas, MD/PhD
Role: PRINCIPAL_INVESTIGATOR
Karolinska University Hospital
Locations
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Skåne University Hospital
Malmo, , Sweden
Örebro University Hospital
Örebro, , Sweden
Sankt Gorans Hospital
Stockholm, , Sweden
Stockholm Southern Hospital
Stockholm, , Sweden
Karolinska University Hospital
Stockholm, , Sweden
Norrlands University Hospital
Umeå, , Sweden
Uppsala University Hospital
Uppsala, , Sweden
Countries
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Central Contacts
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Facility Contacts
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References
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Matikas A, Naume B, Wildiers H, Sonke G, Dieci MV, Karakatsanis A, Andersson A, Barnekow E, Kessler LE, Einbeigi Z, Killander F, Linderholm B, Schiza A, Valachis A, Nearchou A, Engebraaten O, Porojnicu A, Soland MH, Mannsaker B, Raj SX, Blix ES, Nordstrand CS, Lambertini M, Vernieri C, Punie K, Sotiriou C, Bergh J, Villacampa G, Zouzos A, Hellstrom M, Hartman J, Foukakis T. Randomised trial of trastuzumab deruxtecan and biology-driven selection of neoadjuvant treatment for HER2-positive breast cancer: a study protocol of ARIADNE. BMJ Open. 2025 Aug 27;15(8):e102626. doi: 10.1136/bmjopen-2025-102626.
Other Identifiers
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ARIADNE
Identifier Type: -
Identifier Source: org_study_id
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