Trial Title:
Trastuzumab Deruxtecan Versus Standard Neoadjuvant Treatment for HER2-positive Breast Cancer
NCT ID:
NCT05900206
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Paclitaxel
Docetaxel
Cyclophosphamide
Carboplatin
Trastuzumab
Letrozole
Epirubicin
Pertuzumab
Trastuzumab deruxtecan
Conditions: Keywords:
HER2-positive
neoadjuvant treatment
trastuzumab deruxtecan
T-DXd
PAM50
molecular subtype
ribociclib
HER2-enriched
breast cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Parallel, two arms for cycles 1-3. Further treatment (cycles 4-6) decided by molecular
intrinsic subtype.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Trastuzumab deruxtecan
Description:
Experimental drug. Provided in 100mg vials. IV infusion.
Arm group label:
HER2-enriched (cycles 4-6)
Arm group label:
T-DXd (cycles 1-3)
Other name:
T-DXd, Enhertu
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Active comparator. IV infusion.
Arm group label:
HER2-enriched (cycles 4-6)
Arm group label:
Standard treatment (TCHP or PCHP; cycles 1-3)
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Active comparator. IV infusion.
Arm group label:
HER2-enriched (cycles 4-6)
Arm group label:
Standard treatment (TCHP or PCHP; cycles 1-3)
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Active comparator. IV infusion.
Arm group label:
HER2-enriched (cycles 4-6)
Arm group label:
Standard treatment (TCHP or PCHP; cycles 1-3)
Intervention type:
Drug
Intervention name:
Trastuzumab
Description:
Active comparator. IV infusion.
Arm group label:
HER2-enriched (cycles 4-6)
Arm group label:
Standard treatment (TCHP or PCHP; cycles 1-3)
Other name:
Herceptin
Intervention type:
Drug
Intervention name:
Pertuzumab
Description:
Active comparator. IV infusion.
Arm group label:
HER2-enriched (cycles 4-6)
Arm group label:
Standard treatment (TCHP or PCHP; cycles 1-3)
Other name:
PErjeta
Intervention type:
Drug
Intervention name:
Ribociclib
Description:
Experimental drug. Tablets.
Arm group label:
ER-positive and Luminal (cycles 4-6)
Other name:
Kisqali
Intervention type:
Drug
Intervention name:
Letrozole
Description:
Experimental drug. Tablets.
Arm group label:
ER-positive and Luminal (cycles 4-6)
Intervention type:
Drug
Intervention name:
Epirubicin
Description:
Active comparator. IV infusion.
Arm group label:
ER-negative and Luminal, or Basal-like, or Normal-like (cycles 4-6)
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Active comparator. IV infusion.
Arm group label:
ER-negative and Luminal, or Basal-like, or Normal-like (cycles 4-6)
Summary:
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.
Criteria for eligibility:
Criteria:
To be eligible for the study, patients must fulfil all inclusion criteria:
1. Women or men 18 years or older
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
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:
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
To be eligible for the study, patients must not fulfil any exclusion criteria:
1. Participation in other interventional trials
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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Skåne University Hospital
Address:
City:
Malmö
Zip:
21428
Country:
Sweden
Status:
Not yet recruiting
Contact:
Last name:
Fredrika Killander, MD/PhD
Phone:
(0046)046177428
Email:
fredrika.killander@med.lu.se
Facility:
Name:
Sankt Gorans Hospital
Address:
City:
Stockholm
Zip:
11219
Country:
Sweden
Status:
Not yet recruiting
Contact:
Last name:
Luisa Edman Kessler, MD/PhD
Phone:
+46736160284
Email:
luisa.edmankessler@capiostgoran.se
Facility:
Name:
Stockholm Southern Hospital
Address:
City:
Stockholm
Zip:
11861
Country:
Sweden
Status:
Not yet recruiting
Contact:
Last name:
Elin Barnekow, MD
Phone:
(0046)0736565798
Email:
elin.barnekow@regionstockholm.se
Facility:
Name:
Karolinska University Hospital
Address:
City:
Stockholm
Zip:
17164
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Alexios Matikas, MD/PhD
Phone:
+46767823322
Email:
alexios.matikas@regionstockholm.se
Facility:
Name:
Norrlands University Hospital
Address:
City:
Umeå
Zip:
90185
Country:
Sweden
Status:
Not yet recruiting
Contact:
Last name:
Anne Andersson, MD/PhD
Phone:
(0046)0907857887
Email:
anne.andersson@regionvasterbotten.se
Facility:
Name:
Uppsala University Hospital
Address:
City:
Uppsala
Zip:
75185
Country:
Sweden
Status:
Not yet recruiting
Contact:
Last name:
Henrik Lindman, MD/PhD
Phone:
(0046)0706884878
Email:
henrik.lindman@igp.uu.se
Facility:
Name:
Örebro University Hospital
Address:
City:
Örebro
Zip:
70185
Country:
Sweden
Status:
Not yet recruiting
Contact:
Last name:
Antonios Valachis, MD-PhD
Phone:
(0046)0735617691
Email:
antonios.valachis@oru.se
Start date:
October 26, 2023
Completion date:
April 30, 2032
Lead sponsor:
Agency:
Karolinska University Hospital
Agency class:
Other
Source:
Karolinska University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05900206
