Neoadjuvant Study of Pyrotinib and Trastuzumab Plus Vinorelbine in Trastuzumab-refractory HER2-Positive Breast Cancer.
Keywords
Abstract
Description
Neoadjuvant therapy is the standard treatment for locally advanced breast cancer and is used to reduce tumors to make them operable, and to increase breast-conserving rates. In recent years, the anti-HER2 treatment mode, which is double-blocked by a combination of dual-targeted drugs, has obtained clinical approval in adjuvant therapy and neoadjuvant therapy. Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. Based on previous clinical studies, we designed the study to explore the possibility of Pyrotinib in combination with Trastuzumab plus Vinorelbine given as neoadjuvant treatment in HER2 positive early stage or locally advanced breast cancer.
Dates
| Last Verified: | 04/30/2019 |
| First Submitted: | 05/08/2019 |
| Estimated Enrollment Submitted: | 05/08/2019 |
| First Posted: | 05/12/2019 |
| Last Update Submitted: | 05/12/2019 |
| Last Update Posted: | 05/14/2019 |
| Actual Study Start Date: | 05/31/2019 |
| Estimated Primary Completion Date: | 05/31/2020 |
| Estimated Study Completion Date: | 12/29/2020 |
Condition or disease
Intervention/treatment
Drug: Pyrotinib + trastuzumab +Vinorelbine
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Pyrotinib + trastuzumab +Vinorelbine Pyrotinib in Combination With Trastuzumab Plus Vinorelbine | Drug: Pyrotinib + trastuzumab +Vinorelbine Pyrotinib:400mg orally daily Trastuzumab:8mg/kg ivgtt load followed by 6mg/kg ivgtt 3-weekly for a total of 4 cycles Vinorelbine :25mg/m2 ivgtt 3-weekly for a total of 4 cycles,d1 d8 |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | Female |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - 1. female patients, 18 years ≤ age ≤ 75 years. 2. Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1. 3. Histologically confirmed invasive breast cancer:early stage or locally advanced,Primary tumour greater than 2 cm diameter 4. HER2 positive (HER2+++ by IHC or FISH+) 5. Subjects received neoadjuvant therapy with trastuzumab 2 weeks post-imaging evaluation Patients with a price of PD or SD. 6. Known hormone receptor status. 7. Required laboratory values including following parameters: ANC: ≥ 1.5 x 10^9/L;Platelet count: ≥ 100 x 10^9/L;Hemoglobin: ≥ 9.0 g/dL;Total bilirubin: ≤ 1.5 x upper limit of normal (ULN);ALT and AST: ≤ 1.5 x ULN (or ≤ 5×ULN in patients with liver metastases);BUN and creatine clearance rate: ≥ 50 mL/min;LVEF: ≥ 50%;QTcF: < 470 ms for female and < 450 ms for male. 8. Signed the informed consent form prior to patient entry. 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. |
Outcome
Primary Outcome Measures
1. ORR [[Time Frame: Baseline up to cycle 4 (assessed at Baseline, at the time of pre-surgery)up to approximately 12 months]
Secondary Outcome Measures
1. Pathological Complete Response (pCR) [Time Frame: through study completion, an average of 1 year]
2. EFS [Time Frame: Following surgery until Year 5]
3. DFS [Time Frame: Following surgery until Year 5]
4. DDFS [Time Frame: Following surgery until Year 5]
