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Trastuzumab Deruxtecan Versus Standard Neoadjuvant Treatment for HER2-positive Breast Cancer

ConditionBreast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorKarolinska University Hospital

About this trial

The goal of this clinical trial is to compare trastuzumab deruxtecan (T-DXd) to standard preoperative treatment in patients with non-metastatic HER2-positive breast cancer. The main questions it aims to answer are:

* 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Women or men 18 years or older

Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations

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).

Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the time of randomization (see Appendix B).

Disqualifiers

Participation in other interventional trials

Presence of distant metastases, including node metastases in the contralateral thoracic region or in the mediastinum

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.

History of invasive breast cancer

Trial design

Design model

Parallel

Treatments tested in this trial

  • Trastuzumab deruxtecan

    Drug

    Experimental drug. Provided in 100mg vials. IV infusion.

  • Docetaxel

    Drug

    Active comparator. IV infusion.

  • Paclitaxel

    Drug

    Active comparator. IV infusion.

  • Carboplatin

    Drug

    Active comparator. IV infusion.

  • Trastuzumab

    Drug

    Active comparator. IV infusion.

  • Pertuzumab

    Drug

    Active comparator. IV infusion.

  • Ribociclib

    Drug

    Experimental drug. Tablets.

  • Letrozole

    Drug

    Experimental drug. Tablets.

  • Epirubicin

    Drug

    Active comparator. IV infusion.

  • Cyclophosphamide

    Drug

    Active comparator. IV infusion.

Treatment groups

370 Participants
are divided into 5 treatment groups
Group A: T-DXd (cycles 1-3)Experimental treatment 1 intervention
Group B: Standard treatment (TCHP or PCHP; cycles 1-3)Active comparator 5 interventions
Group C: ER-positive and Luminal (cycles 4-6)Other 2 interventions
Group D: ER-negative and Luminal, or Basal-like, or Normal-like (cycles 4-6)Other 2 interventions
Group E: HER2-enriched (cycles 4-6)Other 6 interventions

Trial outcomes

Primary outcomes

1

Pathologic complete response (pCR) of HER2-enriched patients

Locally assessed rate of pCR at the molecularly HER2-enriched population, defined as ypT0/Tis, ypN0, as determined at the surgical specimen by a pathologist blinded to treatment assignment (intention-to-treat analysis)

Time frame
Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days)

Secondary outcomes

1

Pathologic complete response (pCR) of the initially randomized patients

Locally assessed rate of pCR, defined as ypT0/Tis, ypN0, at the two patient groups of the initial randomization of TCHP versus T-DXd, regardless of administered therapy after cycle 3

Time frame
Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days)
2

Event-free survival

Event-free survival (EFS), defined as time from randomization to breast cancer relapse, contralateral breast cancer, other malignant neoplasms, or death by any cause, for each molecular group, including the comparison of TCHP versus T-DXd in HER2-enriched patients, and at the two patient groups of the initial randomization of TCHP versus T-DXd

Time frame
From randomization to event, up to five years
3

Biomarkers

Exploratory analysis of biomarkers of response/resistance to administered neoadjuvant therapy using genomics, transcriptomics and proteomics in both tumor tissue and blood/plasma

Time frame
From randomization to event, up to five years
4

Pathologic complete response (pCR) of ER-positive and luminal patients

Locally assessed rate of pCR at ER-positive and luminal subgroup

Time frame
Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days)

Other outcomes

1

Exploratory biomarkers

Exploratory analyses of clinicopathologic characteristics as predictors for response

Time frame
Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Karolinska University Hospital

Lead sponsor

Source ClinicalTrials.gov
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