Trastuzumab Deruxtecan Versus Standard Neoadjuvant Treatment for HER2-positive Breast Cancer
- Registration Number
- NCT05900206
- Lead Sponsor
- Karolinska University Hospital
- 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?
...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 370
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard treatment (TCHP or PCHP; cycles 1-3) Paclitaxel 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. T-DXd (cycles 1-3) Trastuzumab deruxtecan Trastuzumab Deruxtecan, administered every three weeks for three courses. Further treatment is decided by the intrinsic molecular (PAM50) subtype of the tumor. Standard treatment (TCHP or PCHP; cycles 1-3) Docetaxel 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. Standard treatment (TCHP or PCHP; cycles 1-3) Carboplatin 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. Standard treatment (TCHP or PCHP; cycles 1-3) Trastuzumab 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. ER-positive and Luminal (cycles 4-6) Ribociclib Ribociclib, letrozole, trastuzumab, pertuzumab Standard treatment (TCHP or PCHP; cycles 1-3) Pertuzumab 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. ER-negative and Luminal, or Basal-like, or Normal-like (cycles 4-6) Epirubicin 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. ER-positive and Luminal (cycles 4-6) Letrozole Ribociclib, letrozole, trastuzumab, pertuzumab HER2-enriched (cycles 4-6) Trastuzumab deruxtecan The same treatment with T-DXd or TCHP/PCHP administered every three weeks for three more courses will continue from cycles 1-3 ER-negative and Luminal, or Basal-like, or Normal-like (cycles 4-6) Cyclophosphamide 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. HER2-enriched (cycles 4-6) Docetaxel The same treatment with T-DXd or TCHP/PCHP administered every three weeks for three more courses will continue from cycles 1-3 HER2-enriched (cycles 4-6) Paclitaxel The same treatment with T-DXd or TCHP/PCHP administered every three weeks for three more courses will continue from cycles 1-3 HER2-enriched (cycles 4-6) Carboplatin The same treatment with T-DXd or TCHP/PCHP administered every three weeks for three more courses will continue from cycles 1-3 HER2-enriched (cycles 4-6) Trastuzumab The same treatment with T-DXd or TCHP/PCHP administered every three weeks for three more courses will continue from cycles 1-3 HER2-enriched (cycles 4-6) Pertuzumab The same treatment with T-DXd or TCHP/PCHP administered every three weeks for three more courses will continue from cycles 1-3
- Primary Outcome Measures
Name Time Method Pathologic complete response (pCR) of HER2-enriched patients 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 Outcome Measures
Name Time Method 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) 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
Rates of adverse events During neoadjuvant treatment at the end of each treatment cycle (cycle length 21 days) Frequency and grade of adverse events (AE) (according to NCI CTCAE v. 5.0) and rate of discontinuation due to toxicity
Event-free survival From randomization to event, up to five years 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
Biomarkers From randomization to event, up to five years Exploratory analysis of biomarkers of response/resistance to administered neoadjuvant therapy using genomics, transcriptomics and proteomics in both tumor tissue and blood/plasma
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) Locally assessed rate of pCR at ER-positive and luminal subgroup
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) Locally assessed rate of pCR at ER-negative and luminal subgroup, at the basal-like subgroup and the normal-like subgroup
Objective response rate at three cycles After the completion of three treatment cycles (each cycle is 21 days) Rates of radiologic complete response after three courses of either standard therapy or T-DXd
Overall survival From randomization to event, up to five years Overall survival (OS), defined as time from randomization to 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
Distant relapse-free survival From randomization to event, up to five years Distant relapse-free survival (DRFS), defined as time from randomization to distant metastases 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
Objective response rate at six cycles After the completion of six treatment cycles (each cycle is 21 days) Rates of complete radiologic response, 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
Residual Cancer Burden Categorical outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days) Pathologic response according to Residual Cancer Burden Class 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
Breast conserving surgery Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days) Rate of breast conserving surgery, 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
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) Rate of de-escalation of breast surgery (conversion from mastectomy to breast conserving surgery or de-escalation of complexity from an oncoplastic breast-conserving procedure to simple wide local excisions) 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 randomiz...
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) Rate of Sentinel Lymph Node Dissection (SLND), 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
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) Rate of de-escalation of axillary surgery (conversion from axillary lymph node dissection to either targeted axillary dissection or sentinel lymph node dissection) 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
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 The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale ...
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 The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the ...
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 The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 4 questions about their emotional functioning (Items 21-24) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in t...
Axillary surgery Binary outcome which will be assessed at the time of surgery after six cycles of treatment (each cycle is 21 days) Rate of Sentinel Lymph Node detection, Targeted Axillary Dissection success and false-negative rates of these procedures in initially node-positive patients 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
Trial Locations
- Locations (7)
Stockholm Southern Hospital
🇸🇪Stockholm, Sweden
Skåne University Hospital
🇸🇪Malmö, Sweden
Sankt Gorans Hospital
🇸🇪Stockholm, Sweden
Uppsala University Hospital
🇸🇪Uppsala, Sweden
Karolinska University Hospital
🇸🇪Stockholm, Sweden
Norrlands University Hospital
🇸🇪Umeå, Sweden
Örebro University Hospital
🇸🇪Örebro, Sweden