Chemotherapy-Free pCR-Guided Strategy With Trastuzumab-pertuzumab and T-DM1 in HER2-positive Early Breast Cancer
- Conditions
- Early Breast Cancer
- Interventions
- Registration Number
- NCT04733118
- Lead Sponsor
- MedSIR
- Brief Summary
This is a multicenter, open-label, single-arm, one-stage, phase II study to assess the efficacy of a chemotherapy-free pathological complete response (pCR)-guided strategy with trastuzumab and pertuzumab (given as a subcutaneous fixed-dose combination) and T-DM1, for patients with previously untreated HER2-positive early breast cancer.
- Detailed Description
Patients ≥ 18 years of age with previously untreated HER2 IHC 3+ invasive carcinoma according to ASCO/CAP 2018 guidelines.
Tumor size between \>5 to 30 mm by breast MRI and node-negative status by clinical exam, MRI, and ultrasound. In patients with suspected axillary node involvement, a negative fine needle aspiration biopsy (FNAB) will be mandatory.
Central review for:
Breast MRI. HER2 status. Neoadjuvant treatment will consist In 8 cycles of fixed-dose subcutaneous (SC FDC) HP combination (± ET according to HR status).
urgery will be performed within 4 weeks from the last cycle of HP (sentinel node biopsy will be mandatory; subsequent axillary dissection will be performed according to local guidelines). Surgery will require free margins for any infiltrating or DCIS lesion.
Radiotherapy will be mandatory for patients with breast preservation.
Adjuvant systemic therapy will be started within 4 weeks from surgery depending on pathological report:
Arm A: pCR (breast and axilla): HP SC FDC x 10 cycles. Arm B: Residual invasive breast tumor and/or ypN0(i+), ypN0(mol+), ypN1mi: T-DM1 x 10 cycles Arm C: ypN1 to N3: T-DM1 x 10 cycles, with physician's choice chemotherapy allowed between surgery and T-DM1.
All patients with HR\[+\] tumors will receive adjuvant ET up to at least 5 years (ET will also be administered in association with adjuvant HP or T-DM1, with the exception of the cycles involving the use of chemotherapy in Arm C).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 393
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Patient HER 2+ IHC 3+ Trastuzumab and Pertuzumab (FDC SC) and T-DM1 Patients ≥18 years of age with previously untreated HER2-positive (HER2\[+\]) (Immunohistochemistry \[IHC\] 3+) invasive carcinoma according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria and tumor size between \>5 to 25 mm by breast magnetic resonance imaging (MRI) and node-negative status by clinical exam, MRI, and ultrasound. Patients must have not been previously treated with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy (ET) for invasive breast cancer. Patients with metastatic disease are not eligible. In patients with suspected axillary node involvement, a negative fine needle aspiration biopsy (FNAB) will be mandatory
- Primary Outcome Measures
Name Time Method 3-year recurrence-free interval (3y-RFI) 3 years 3-year recurrence-free interval (3y-RFI) defined as time from start of treatment in adjuvant setting until recurrence, new invasive disease, or death from breast cancer. Recurrence will be defined in accordance with the standardized efficacy endpoints (STEEP) criteria.
Global health status decline 1 year Global health status decline rate at 1 year from start of neoadjuvant treatment, defined as the rate of patients with a ≥10% global health status decline at 1 year from start of neoadjuvant treatment as assessed by the Global Health Status/QoL EORTC-QLC-C30 scale and its breast cancer module QLQ-BR23.
- Secondary Outcome Measures
Name Time Method Survival rates invasive disease-free survival (iDFS) 3 years and 5 years Analyze iDFS
Survival rates EFS 3 years and 5 years Analyze the event-free survival (EFS)
Health-Related Quality of Life (HRQoL) - QLQ-BR23 Baseline up to 5 years Change from baseline in scores using the European Organisation for Research and Treatment of Cancer QLQ-BR23 \[with 4 functional and 4 symptom scales\], at baseline, Day 1 of cycles 2-4, then on Day 1 of each subsequent cycle starting with cycle 6, and at the end-of-treatment. Responses to all items are converted to a 0-100 scale using a standard scoring algorithm. For functional scales, higher score represents a better level of functioning; for symptom scales, a higher score represents a higher severity of symptoms.
pathological complete response (pCR) after neoadjuvant treatment (8 cycles, an average of 6months) pCR rates concerning breast and lymph nodes (pCRBREAST+LYMPH NODE) and pCR concerning breast only (pCRBREAST) in the overall population.
Breast-conserving surgery (BCS) after neoadjuvant treatment (8 cycles, an average of 6months) Evaluate the rate of BCS
Response rate BCS after neoadjuvant treatment (8 cycles, an average of 6months) Evaluate the correlation between final MRI-guide response rate results and breast-conserving surgery (BCS)
Response rate pCR after neoadjuvant treatment (8 cycles, an average of 6months) Evaluate the correlation between final MRI- guide response rate and pCR
Survival rates relapse-free interval (RFI) 5 years Analyze RFI
To evaluate the ratio of patients who have needed chemotherapy. before T-DM1 Ratio of patients of cohort C who will receive adjuvant chemotherapy before T-DM1.
pathological complete response (pCR) according to hormone receptor (HR) status after neoadjuvant treatment (8 cycles, an average of 6months) pCR rates according to HR status
Residual cancer burden (RCB) after neoadjuvant treatment (8 cycles, an average of 6months) RCB -0, -I, -II, -III; (0:best outcome, III: worst outcome)
Survival rates relapse-free survival (RFS) 3 years and 5 years Analyze RFS
Survival rates disease-free survival (DFS) 3 years and 5 years Analyze DFS
Health-Related Quality of Life (HRQoL) - QLQ-C30 Baseline up to 5 years Change from baseline in scores using the European Organisation for Research and Treatment of Cancer QoL Questionnaire Core 30 (QLQ-C30) \[with 5 functional and 3 symptom scales, a Global Health Status (GHS)/QoL scale, and 6 single items\], at baseline, Day 1 of cycles 2-4, then on Day 1 of each subsequent cycle starting with cycle 6, and at the end-of-treatment. Responses to all items are converted to a 0-100 scale using a standard scoring algorithm. For functional scales, higher score represents a better level of functioning; for symptom scales, a higher score represents a higher severity of symptoms.
Response rate RCB after neoadjuvant treatment (8 cycles, an average of 6months) Evaluate the correlation between final MRI -guide response rate and RCB at surgery
Survival ratesdistant relapse-free survival (DRFS) 3 years and 5 years Analyze DRFS
Safety adverse events (AEs) Baseline up to 5 years Number of patients with treatment-related AEs (Grade 3 and 4 AEs and serious adverse events \[SAEs\]) by using the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.
Survival rates overall survival (OS) 3 years and 5 years Analyze OS
Survival ratesbreast cancer-specific survival (BCSS). 3 years and 5 years Analyze BCSS
To assess the cardiac toxicity profile after 1 year of adjuvant treatment after 1 year of adjuvant treatment Adverse events of cardiotoxicity after 1 year of adjuvant treatment according to the NCI-CTCAE v.5.0.
To assess the general toxicity profile according to CTCAE v.5.0. at 3 and 5 year Toxicity and safety profile at 3 and 5 years as per NCI-CTCAE v.5.0.
Related Research Topics
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Trial Locations
- Locations (41)
Hospital Universitari San Joan de Reus
🇪🇸Reus, Tarragona, Spain
Tolna County Balassa János Hospital
🇭🇺Szekszárd, Hungary
Praxisnetzwerk Hämatologie und intern. Onkologie
🇩🇪Cologne, Germany
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S.Orsola-Malpighi
🇮🇹Bologna, Italy
AO Ospedale Civile Legnano
🇮🇹Milan, Italy
UMHAT Sveti Ivan Rilski EAD Department of Medical Oncology
🇧🇬Sofia, Bulgaria
Evangelisches Krankenhaus Bethesda
🇩🇪Duisburg, Germany
Kliniken Essen Mitte
🇩🇪Essen, Germany
Universitätsklinikum Essen Frauenklinik
🇩🇪Essen, Germany
Universitätsklinikum Mannheim GmbH
🇩🇪Manheim, Germany
Klinikum Ernst von Bergmann
🇩🇪Potsdam, Germany
Békés county hospital
🇭🇺Békés, Hungary
Istituto Europeo di Oncologia - NC
🇮🇹Milan, Italy
Ospedale San Gerardo
🇮🇹Monza, Italy
Azienda Ospedaliero-Universitaria di Parma
🇮🇹Parma, Italy
Ospedale Guglielmo da Saliceto
🇮🇹Piacenza, Italy
Fondazione Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
ICO L'Hospitalet - Instituto Catalán de Oncología
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Cordoba, Spain
Hospital Universitario A Coruña
🇪🇸A Coruna, Spain
Centro Oncológico de Galicia
🇪🇸A Coruña, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital Universitari Dexeus - Grupo Quirónsalud
🇪🇸Barcelona, Spain
Institut Català d' Oncologia Badalona (ICO)
🇪🇸Badalona, Spain
VHIO Vall d'Hebron Institute of Oncology
🇪🇸Barcelona, Spain
Hospital Universitario de Basurto
🇪🇸Bilbao, Spain
Consorcio Hospitalario Provincial De Castelló
🇪🇸Castelló De La Plana, Spain
Hospital Universitario Clínico San Cecilio de Granada
🇪🇸Granada, Spain
Complejo Hospitalario de Jaen
🇪🇸Jaen, Spain
Complejo Asistencial Universitario de León
🇪🇸León, Spain
Hospital Universitari Arnau de Vilanova de Lleida
🇪🇸Lleida, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Quirón San Camilo- Ruber Juan Bravo
🇪🇸Madrid, Spain
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario de Torrejón
🇪🇸Torrejón, Spain
Instituto Valenciano de Oncología (IVO)
🇪🇸Valencia, Spain
Hospital La Fe
🇪🇸Valencia, Spain
Consorcio Hospital General de Valencia
🇪🇸Valencia, Spain
Hospital Arnau de Vilanova de Valencia
🇪🇸Valencia, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain