Pyrotinib Rechallenge in Her2-positive Metastatic Breast Cancer Pretreated With Pyrotinib and Trastuzumab

Study Overview
=================
Brief Summary
-----------------
Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This study is a randomized, open-label, multi-center, parallel design study of the combination of pyrotinib, trastuzumab and chemotherapy versus trastuzumab and chemotherapy in HER2+ MBC patients, who have prior received trastuzumab and pyrotinib. Patients will be randomized in a 2:1 ratio to one of the following treatment arms. Arm A: pyrotinib + trastuzumab + chemotherapy, Arm B: trastuzumab + chemotherapy. Patients will receive either arm of therapy until disease progression, unacceptable toxicity, or withdrawal of consent.

Official Title
-----------------
Pyrotinib Rechallenge in Her2-positive Metastatic Breast Cancer Pretreated With Pyrotinib and Trastuzumab

Conditions
-----------------
HER2-positive Breast Cancer, Metastatic Breast Cancer

Intervention / Treatment
-----------------
* Drug: Trastuzumab plus chemotherapy
* Drug: Trastuzumab in combination with pyrotinib plus chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged ≥18 and ≤75 years; Pathologically confirmed HER2 positive patients with recurrence/ metastatic breast cancer: HER2 IHC 3+, or HER2 IHC 2+ and FISH detection gene amplification; History of trastuzumab-containing chemotherapy in neoadjuvant, adjuvant or recurrence/ metastatic setting; History of pyrotinib-containing chemotherapy in neoadjuvant or recurrence/ metastatic setting; Previously reveived ≤2 systemic treatment in recurrence/ metastasis setting; (anti-HER2 ADCs such as T-DM1 is included in chemotherapy regimens, endocrine therapy alone is not included); ECOG performance status of 0 to 1; According to RECIST 1.1, at least one extracranial measurable lesion exists； Signed informed consent. Exclusion Criteria: Patients with leptomeningeal metastasis or unstable brain metastasis; History of neurological or psychiatric disorders; Second malignancies within 5 years, except for cured skin basal cell carcinoma, carcinoma in-situ of uterine cervix and squamous-cell carcinoma; Undergone major surgical procedures or significant trauma within 4 weeks prior to randomization, or expected to undergo major surgery. Factors influencing the usage of oral administration (e.g. unable to swallow, chronic diarrhea and intestinal obstruction, etc.); History of allergies to the drug components of this regimen; History of Immunodeficiency, acquired or congenital immunodeficiency (HIV positive), history of organ transplantation; Any other situations judged by investigator as not suitable for participating in this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Trastuzumab plus chemotherapy<br> | Drug: Trastuzumab plus chemotherapy<br>* Trastuzumab: 8 mg/kg loading dose followed by 6 mg/kg, Q3W Chemotherapy regimen is chosen from the following: Vinorelbine, Gemcitabine, taxanes or Eribulin monotherapy Experimental: Pyrotinib +Trastuzumab + chemotherapy<br>|
| Experimental: Pyrotinib in combination with Trastuzumab plus chemotherapy<br> | Drug: Trastuzumab in combination with pyrotinib plus chemotherapy<br>* Pyrotinib: 400 mg po QD, Q3W Chemotherapy regimen is chosen from the following: Vinorelbine, Gemcitabine, taxanes or Eribulin monotherapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) |  | approximately 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | approximately 8 months | 
| Adverse Events (AEs) |  | From the first drug administration to within 28 days for the last treatment |