Breast Cancer, Breast Diseases, Neoplasm, Breast
Conditions
Brief summary
This is a randomized, double-blind multicenter Phase III study for evaluating the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus docetaxel and Carboplatin versus placebo and trastuzumab plus docetaxel and Carboplatin given as neoadjuvant treatment in HER2 positive early stage or locally advanced breast cancer.
Detailed description
The investigators hypothesized that the experimental group (Pyrotinib+Trastuzumab+Docetaxel+ Carboplatin) could have a higher Pathological Complete Response (pCR) rate than the control group (Placebo +Trastuzumab+Docetaxel+ Carboplatin) in neoadjuvant chemotherapy. It is proposed that 100 participants will be enrolled in this study. The target population is women with early breast cancer (stage of T1-4N0-3M0) who are eligible for primary systemic therapy. The primary objective of the trial is to determine the pCR rate. The secondary objective of the trial is to determine the Event-free survival(EFS), Disease-free Survival (DFS), Distance Disease-free Survival (DDFS), Objective Response Rate (ORR) rate.
Interventions
DRUGPyrotinib
Pyrotinib: 400mg orally daily
DRUGTrastuzumab
Trastuzumab:8mg/kg iv load followed by 6mg/kg iv 3-weekly for a total of 6 cycles;
DRUGDocetaxel
Docetaxel: 75mg/m2 for a total of 6 cycles
DRUGCarboplatin
Carboplatin: AUC=5 for a total of 6 cycles
DRUGPlacebo Oral Tablet
Placebo Oral Tablet: 400mg orally daily
Sponsors
Zhejiang Cancer Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Experimental: Pyrotinib (400mg orally daily)+Trastuzumab (8mg/kg iv load followed by 6mg/kg iv 3-weekly)+Docetaxel (75mg/m2)+ Carboplatin(AUC=5), for a total of 6 cycles. Placebo Comparator: Placebo Oral Tablet (400mg orally daily)+Trastuzumab (8mg/kg iv load followed by 6mg/kg iv 3-weekly)+Docetaxel (75mg/m2)+ Carboplatin(AUC=5), for a total of 6 cycles.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. female patients, 18 years ≤ age ≤ 80 years； 2. Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1 3. Histologically confirmed invasive breast cancer（early stage or locally advanced） 4. HER2 positive (HER2+++ by IHC or FISH+) 5. Known hormone receptor status. 6. Cardiovascular: Baseline left ventricular ejection fraction (LVEF)≥55% measured by ECHO 7. Signed informed consent form (ICF)
Exclusion criteria
1. Metastatic disease (Stage IV) or inflammatory breast cancer 2. Previous or current history of malignant neoplasms, except for curatively treated: Basal and squamous cell carcinoma of the skin, Carcinoma in situ of the cervix. 3. Clinically relevant cardiovascular disease: Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension ≥180/110); 4. Unable or unwilling to swallow tablets.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pCR | through study completion, an average of 1 year | Percentage of Participants With Pathological Complete Response (pCR) at the Time of Surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EFS | Following surgery until Year 3 | Event-free survival |
| DFS | Following surgery until Year 3 | Disease-free Survival |
| DDFS | Following surgery until Year 3 | Distance Disease-free Survival |
| ORR | Baseline up to cycle 4 (assessed at Baseline, at the time of pre-surgery)up to approximately 12 months | Objective Response Rate |
Countries
China
Contacts
Primary ContactDing Xiaowen, DR.
Backup ContactDing Yuqin
Outcome results
None listed