Breast Cancer Early Stage Breast Cancer (Stage 1-3)
Conditions
Keywords
Breast Cancer, HER2-positive Breast Cancer, pathologic complete response, SHR-A1811, Pertuzumab, Albumin-Paclitaxel
Brief summary
The goal of this clinical trial is to evaluate the efficacy and safety of SHR-A1811 plus pertuzumab in combination with or without albumin-paclitaxel neoadjuvant therapy for early or locally advanced HER2-positive breast cancer. The main questions it aims to answer are: * Does the pCR of SHR-A1811 plus pertuzumab with or without albumin-paclitaxel improve compared to the current standard of treatment? * Is the safety of SHR-A1811 plus pertuzumab with or without albumin-paclitaxel better compared to the current standard of treatment? Researchers will compare SHR-A1811+pertuzumab or SHR-A1811+pertuzumab+albumin-paclitaxel to TCbHP to see if SHR-A1811 plus pertuzumab with or without albumin-paclitaxel works to treat early or locally advanced HER2-positive breast cancer. Subjects will be randomly assigned 1:1:1 to： * cohort 1：SHR-A1811 combined with pertuzumab for 6 cycles; * cohort 2：SHR-A1811 combined with pertuzumab and albumin-paclitaxel for 6 cycles; * cohort 3：TCbHP (docetaxel, carboplatin, trastuzumab and pertuzumab) for 6 cycles. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, questionnaires, and scans.
Interventions
DRUGSHR-A1811
an anti-HER2 antibody-drug conjugate (ADC)
DRUGPertuzumab
Pertuzumab
Nab paclitaxel
DRUGDocetaxel
Docetaxel
DRUGCarboplatin
Carboplatin
DRUGTrastuzumab
Trastuzumab
Sponsors
Henan Cancer Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Non
Intervention model description
Patients who meet the inclusion criteria were randomly divided into SHR-A1811+pertuzumab and SHR-A1811+pertuzumab+albumin-paclitaxel and TCbHP group in a 1:1:1 ratio.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18-70 years old, ECOG 0-1 point. * Clinical T2-T4, with any LN, M0. * HER2+, invasive breast cancer confirmed by histopathology;(HER2 positive expression means that there is at least one case of tumor cell immunohistochemical staining intensity of 3+or positive confirmed by fluorescence in situ hybridization \[FISH\] in the pathological test/review of the primary focus conducted by the Pathology Department of the Research Center Hospital). * Having clinically measurable lesions: measurable lesions displayed on ultrasound, mammography, or MR (optional) within the first month of randomization. * Organ and bone marrow function tests within one month before chemotherapy indicate no contraindications to chemotherapy：Absolute value of neutrophil count ≥ 1.5 × 10\^9/L; Hemoglobin ≥ 90g/L; Platelet count ≥ 100 × 10\^9/L; Total bilirubin≤1.5 ULN (upper limit of normal value); Creatinine≤1.5 × ULN; AST/ALT ≤ 2.5 × ULN. * Cardiac ultrasound: Left ventricular ejection fraction (LVEF ≥ 50%). * Women of childbearing age tested negative for serum pregnancy test 7 days before randomization. * Sign an informed consent form.
Exclusion criteria
* Stage IV (metastatic) breast cancer. * Has received chemotherapy, endocrine therapy, targeted therapy, reflex therapy, etc. for this disease. * The patient has a second primary malignant tumor, except for fully treated skin cancer. * The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or the patient has not fully recovered from such surgical procedures. * The presence of uncontrolled cardiovascular and cerebrovascular disease, including (but not limited to) any of the following within the 6 months prior to the first dose: congestive heart failure (NYHA III or IV), myocardial infarction or cerebral infarction, pulmonary embolism, unstable angina, or arrhythmia requiring treatment at the time of screening; Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restricted cardiomyopathy, undefined cardiomyopathy); A clinically significant history of prolonged QTc, grade II type II atrioventricular block or grade III atrioventricular block or QTc interphase (F method) \> 470 msec (female); Atrial fibrillation (EHRA grade ≥2b); Unmanageable hypertension, which the investigators judged unsuitable for study participation. * Due to serious and uncontrollable other medical diseases, researchers believe that there are contraindications to chemotherapy. * Individuals with a known history of allergies to the drug components of this protocol; * Having a history of immunodeficiency, including HIV testing positive, or suffering from other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response rate (pCR rate) | After surgery（within 1 month） | After neoadjuvant chemotherapy and surgery, the resected specimen (breast + axilla) was free of any invasive cancer (ie, ypT0/is, ypN0) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Disease Free Survival of 5 years | 5-year | 5-year Invasive Disease-Free Survival was defined as patients who did not experience regional, contralateral or distant recurrence, or dies during a follow-up period of at least 5 years from the date of surgery. |
| Event-Free Survival of 5 years | 5-year | 5-year Event-Free Survival was defined as patients who did not experience disease progression during neoadjuvant therapy, local or distant recurrence, second primary malignancy (breast or other cancer), or dies during a follow-up period of at least 5 years after treatment. |
| Objective Response Rate (ORR) | During neoadjuvant therapy before surgery（within 6 months） | ORR is the proportion of patients whose tumors have shrunk significantly over the course of treatment. Specifically, ORR includes both partial response (PR) and complete response (CR). Partial response (PR) : The maximum diameter or volume of the tumor is reduced by at least 30%, but it does not completely disappear. Complete response (CR) : The tumor disappears completely and no visible signs of cancer are confirmed by imaging tests, such as CT scans, MRI, or ultrasound. |
| Adverse Events rate | 2-year | Evaluate the nature, incidence and severity of chemotherapy adverse events according to CTCAE 5.0 |
Countries
China
Contacts
Primary ContactZhenzhen Liu
Outcome results
None listed