Pyrotinib in Combination With Fulvestrant in Patients With HER2 Positive，HR-Positive Metastatic Breast Cancer

Study Overview
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Brief Summary
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HR+/HER2+（Human epidermal growth factor receptor 2 positive and hormone receptor positive）metastatic breast cancer is a special subtype of HER2+breast cancer. Conventional guidelines recommend chemotherapy combined with trastuzumab targeted therapy for this subtype of patients. However, the choice of treatment for these patients after treatment progress is a research hotspot in this field. Pyrotinib is a new class I small molecule Tyrosine kinase inhibitors（TKI） drug with high efficacy and low toxicity after the progress of trastuzumab therapy. Fulvestrant is the most preferred single-drug therapy for HR + metastatic breast cancer recommended unanimously by the guidelines, and fulvestrant and small molecule TKI have synergistic effects. Therefore, we envisage that fulvestrant combined with Pyrotinib in the treatment of HR+/HER2+ metastatic breast cancer in clinical practice has the advantages of improving efficacy and survival. To this end, we intend to conduct a prospective, multi-center, phase II clinical trial to evaluate the efficacy and safety of erlotinib in combination with fulvestrant in patients with human epidermal growth factor receptor 2 (HER2) positive，hormone receptor-positive metastatic breast cancer.

Official Title
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Phase II Study of Pyrotinib in Combination With Fulvestrant in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive，Hormone Receptor（HR）-Positive Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Pyrotinib combined with fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed HER2 positive, hormone receptor-positive patients with locally advanced or metastatic breast cancer: HER2 IHC 3+, or HER2 IHC 2+ and FISH detection gene amplification, ER（estrogen receptor） and/or PR（progesterone receptor） Immunohistochemical staining of more than 10% tumor cells) Aged ≥18 and ≤70 years. ECOG（Eastern Cooperative Oncology Group） performance status of 0 to 1. The life expectancy of more than 12 weeks; At least one measurable lesion exists(RECIST 1.1，Response Evaluation Criteria in Solid Tumors ), or only bone metastasis. Previous neoadjuvant or adjuvant use of trastuzumab, but the disease-free interval between the end of the last trastuzumab and the progression of tumors was more than 12 months Trastuzumab has not been treated in the past or only received first-line treatment for metastatic diseases. It is required that previous (neo) adjuvant or endocrine therapy be given to patients, and that progress of the disease occur during or after treatment. Patients with adequate organ function before enrollment: Neutrophil granulocyte≥1.5×10^9/L Platelet≥100×10^9/L Hemoglobin≥90 g/L Signed informed consent. Exclusion Criteria: Patients who have not received trastuzumab, chemotherapy or endocrine therapy before; Patients with visceral crisis; Patients unable to swallow, with chronic diarrhea, intestinal obstruction, or multiple factors that affect drug use and absorption; Patients with malignant serous effusion which cannot be controlled by drainage or other methods; Less than 4 weeks from the last treatment in the last clinical trial; Receiving any other antitumor therapy; History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent; Patients with serious heart disease; Allergy to Pyrotinib; the history of immunodeficiency； Known history of neurological or psychiatric disease, including epilepsy or dementia; Patients during pregnancy or lactation, patients with childbearing potential tested positive in a baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial; Evidence of significant medical illness that will substantially increase the risk of the participation or completion of the study in the investigator's judgment. Examples included, but not limited to, hypertension, severe diabetes, etc; Patients not eligible for this study judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyrotinib plus fulvestrant<br>Pyrotinib(400 mg once daily) + fulvestrant (500 mg, administered on days 0, 14 (plus or minus 3 days), 28 (plus or minus 3 days), and every 28 (plus or minus 3 days) days) | Drug: Pyrotinib combined with fulvestrant<br>* Pyrotinib 400 mg once daily; Fulvestrant 500 mg administered on days 0, 14 (plus or minus 3 days), 28 (plus or minus 3 days), and every 28 (plus or minus 3 days) days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | From enrollment to progression or death (for any reason) | Estimated 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Ratio of CR and PR in all subjects | Estimated 12 months | 
| Clinical Benefit rate (CBR) | Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects | Estimated 12 months | 
| Overall Survival (OS) | From enrollment to death (for any reason) | Estimated 24 months | 
| Adverse Events and Serious Adverse Events | Safety | From informed consent through 28 days following treatment completion | 
| Efficacy correlation biomarkers | Next Generation Gene Sequencing（NGS） detection of tissue specimens to obtain information on drug sensitivity-related biomarkers , eg, PIK3CA, PTEN, TMB，ESR1，ESR2 | Estimated 12 months | 
| the quality of life | All patients need to fill in the Functional Assessment of Cancer Therapy-Breast (FACT-B), a 44-item self-report instrument designed to measure multidimensional quality of life (QL) in patients with breast cancer. | Estimated 24 months |