A Randomized Trial of Trastuzumab Deruxtecan and Biology-Driven Selection of Neoadjuvant Treatment for HER2-positive Breast Cancer: ARIADNE
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 370
- Locations
- 7
- Primary Endpoint
- Pathologic complete response (pCR) of HER2-enriched patients
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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
Intervention: Trastuzumab (Drug)
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.
Intervention: Pertuzumab (Drug)
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.
Intervention: Trastuzumab (Drug)
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.
Intervention: Carboplatin (Drug)
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.
Intervention: Docetaxel (Drug)
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.
Intervention: Trastuzumab deruxtecan (Drug)
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
Intervention: Carboplatin (Drug)
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
Intervention: Docetaxel (Drug)
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.
Intervention: Cyclophosphamide (Drug)
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.
Intervention: Paclitaxel (Drug)
ER-positive and Luminal (cycles 4-6)
Ribociclib, letrozole, trastuzumab, pertuzumab
Intervention: Ribociclib (Drug)
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.
Intervention: Epirubicin (Drug)
ER-positive and Luminal (cycles 4-6)
Ribociclib, letrozole, trastuzumab, pertuzumab
Intervention: Letrozole (Drug)
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
Intervention: Trastuzumab deruxtecan (Drug)
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
Intervention: Paclitaxel (Drug)
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
Intervention: Pertuzumab (Drug)
Outcomes
Primary Outcomes
Pathologic complete response (pCR) of HER2-enriched patients
Time Frame: Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days)
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)
Secondary Outcomes
- Pathologic complete response (pCR) of the initially randomized patients(Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days))
- Event-free survival(From randomization to event, up to five years)
- Biomarkers(From randomization to event, up to five years)
- Pathologic complete response (pCR) of ER-positive and luminal patients(Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days))
- Pathologic complete response (pCR) of ER-negative and luminal, basal-like and normal-like patients(Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days))
- Objective response rate at three cycles(After the completion of three treatment cycles (each cycle is 21 days))
- Overall survival(From randomization to event, up to five years)
- Distant relapse-free survival(From randomization to event, up to five years)
- Objective response rate at six cycles(After the completion of six treatment cycles (each cycle is 21 days))
- Residual Cancer Burden(Categorical outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days))
- Breast conserving surgery(Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days))
- De-escalation of breast surgery(Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days))
- Sentinel Lymph Node Dissection(Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days))
- De-escalation of axillary surgery(Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days))
- Rates of adverse events(During neoadjuvant treatment at the end of each treatment cycle (cycle length 21 days))
- Change From Baseline in Global Health Status/Quality of Life Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in all participants(During neoadjuvant treatment (before first treatment and after three cycles, 21-day cycles), at the end of treatment (after six 21-day cycles), one year post-surgery and five years post-surgery)
- Change From Baseline in Physical Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in all participants(During neoadjuvant treatment (before first treatment and after three cycles, 21-day cycles), at the end of treatment (after six 21-day cycles), one year post-surgery and five years post-surgery)
- Change From Baseline in Emotional Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in all participants(During neoadjuvant treatment (before first treatment and after three cycles, 21-day cycles), at the end of treatment (after six 21-day cycles), one year post-surgery and five years post-surgery)
- Axillary surgery(Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days))
Investigators
Theodoros Foukakis
Associate Professor
Karolinska University Hospital