A Study of SHR6390 in Combination With Fulvestrant in Patients With HR Positive and HER2 Negative Advanced Breast Cancer

Study Overview
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Brief Summary
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This is a phase III clinical trial to evaluate the efficacy and safety of SHR6390 in combination with Fulvestrant versus placebo combined with Fulvesrant in Patients who have HR positive and HER2 negative recurrent/metastatic breast cancer and have received prior endocrine therapy are eligible for study.

Official Title
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A Phase III Study to Evaluate the Efficacy and Safety of SHR6390 in Combination With Fulvestrant Versus Placebo Combined With Fulvesrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: SHR6390
* Drug: Placebo
* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has the pathologically-confirmed diagnosis of locally recurrent or metastatic, hormone-receptor positive, HER2 negative Breast Cancer. Age: 18 - 75 years old, postmenopausal women or prepostmenopausal women Received prior endocrine therapy One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy. Eastern Cooperative Oncology Group [ECOG] 0-1 Exclusion Criteria: Patients who received prior treatment with any CDK4/6 inhibitor, everolimus or fulvestant. Clinically significant cardiovascular and cerebrovascular diseases,including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, Congestive heart failure (New York heart association (NYHA) class > 2), or ventricular arrhythmia which need medical intervention.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR6390 + Fulvestrant<br>Intervention Drug: SHR6390, Fulvestrant | Drug: SHR6390<br>* SHR6390 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment<br>Drug: Fulvestrant<br>* Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease<br>|
| Placebo Comparator: Placebo + Fulvestrant<br>Intervention Drug: Placebo, Fulvestrant | Drug: Placebo<br>* Placebo 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment<br>Drug: Fulvestrant<br>* Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed PFS | Investigator-assessed Progression Free Survival | Up to approximately 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) per RECIST 1.1 | PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurs first. | Up to approximately 24 months. | 
| OS | Overall Survival | Up to approximately 2 years | 
| ORR | Objective Response Rate | Up to approximately 24 months. | 
| DoR | Duration of Objective Response | Up to approximately 24 months | 
| CBR | Clinical Benefit rate | Up to approximately 24 months. | 
| AEs and SAEs | Number of Participants With adverse events (AEs) and serious adverse events (SAEs) Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03. | Up to approximately 24 months. | 
| Ctrough | Ctrough | Up to 4 weeks |