Dalpiciclib in Combination With Exemestane and Trastuzumab Plus Pyrotinib in Early Triple Positive Breast Cancer

Study Overview
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Brief Summary
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This is a phase II open-label, multicenter trial assessing the efficacy of combination regimenDalpiciclib plus Exemestane plus trastuzumab plus pyrotinibin early triple positive breast cancer patients.

Detailed Description
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This is a phase II open-label, multicenter trial. The study assesses the treatment of patients with ER-positive /HER2 positive early breast cancer with neoadjuvant Dalpiciclib in Combination With Exemestane and Trastuzumab plus Pyrotinib. Patients were treated with intravenous trastuzumab (8 mg/kg loading dose followed by 6 mg/kg, Q3W) for six cycles plus oral Dalpiciclib (125 mg QD x 21，Q4W) and Exemestane (25 mg po QD ）and oral pyrotinib (320 mg po QD) for 20 weeks. The primary endpoints was pathological complete response.

Official Title
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Phase II Open-label, Multicentre, Exploratory Trial of Neoadjuvant Dalpiciclib in Combination With Exemestane and Trastuzumab Plus Pyrotinib in Early Triple Positive Breast Cancer

Conditions
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Breast Cancer, Estrogen Receptor Positive Tumor, HER2-positive Breast Cancer

Intervention / Treatment
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* Drug: Trastuzumab Pyrotinib Exemestane Dalpiciclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 Years to 75 Years Newly diagnosed clinical stage II or III ER+/HER2+ breast cancer, staging criteria is to be based on AJCC 7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Primary tumor must have positive estrogen receptor (ER) ≥10% Primary tumor must be HER2-positive (IHC 3+ or FISH/CISH amplification) Baseline LVEF ≥50% measured by Echocardiography (preferred) or MUGA scan Normal organ and marrow function Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to randomization. Baseline corrected QT interval (QTcF) < 480 ms All patients must be female. Exclusion Criteria: Inflammatory breast cancer Evidence of bilateral invasive breast cancer or metastatic disease Received any prior treatment for primary invasive breast cancer Pregnant or lactating women Abnormal baseline hematological values: Abnormal baseline liver function, bilirubin, creatinine and/or INR (international normalized ratio) Subjects with known infection with HIV, HBV, HCV Other investigational drugs while on study Severe or uncontrolled hypertension, history of congestive heart failure or severe coronary arterial disease. Subjects assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

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

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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: Dalpiciclib in combination with exemestane and trastuzumab plus pyrotinib<br>Patients are treated with intravenous trastuzumab (8 mg/kg loading dose followed by 6 mg/kg, Q3W) for six cycles plus oral Dalpiciclib (125 mg QD x 21，Q4W) and Exemestane (25 mg po QD ）and oral pyrotinib (320 mg po QD) for 20 weeks. | Drug: Trastuzumab Pyrotinib Exemestane Dalpiciclib<br>* Early triple positive breast cancer patients receive combination regimen of Dalpiciclib in Combination With Exemestane and Trastuzumab plus pyrotinib<br>* Other names: Herceptin Pyrotinib Aromasin Dalpiciclib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathological complete response (pCR) | Assess the rate of pathological complete response (pCR) defined as ypT0-ypTis ypN0 at surgery | at surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serial measures of Ki67 | Changes in Ki67 scores from baseline before therapy, 2 weeks after and then at surgery | baseline before therapy, 2 weeks after and at surgery | 
| Objective response | Defined as the number of patients with partial or complete response according to RECIST 1.1 | Tumour assessments will be performed by ultrasound and mammography at screening (prior to start of treatment), and before surgery, an expected average of 24 weeks |