Famitinib Plus SHR6390 and Endocrine Therapy in the Treatment of HR-positive, HER2-negative Advanced Breast Cancer

Study Overview
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Brief Summary
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The main purpose of this study was to evaluate the efficacy and safety of treatment with famitinib plus SHR6390 and endocrine therapy for hormone receptor (HR)-positive, Human Epidermal Growth Factor Receptor (HER) 2 - negative advanced breast cancer.

Detailed Description
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This study would enroll patients with hormone receptor (HR)-positive, Human Epidermal Growth Factor Receptor (HER) 2 - negative advanced breast cancer, aimed to evaluate the efficacy and safety of treatment with famitinib combined with SHR6390 and endocrine therapy.

Official Title
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Study to Evaluate the Efficacy and Safety of Famitinib Plus SHR6390 and Endocrine Therapy in the Treatment of Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer

Conditions
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Metastatic Breast Cancer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Local recurrent or metastatic breast cancer unsuitable for chemotherapy, confirmed histologically. HR-positive, HER2- negative breast cancer(according to 2018 ASCO/CAP HER2 test guideline). Ib: Patients who received no more than 2 line of chemotherapy in advanced setting were recruited; II: Patients who had not received any chemotherapy and no more than 1 line of endocrine therapy. 18-75 years old. Eastern Cooperative Oncology Group (ECOG) performance status 0～1. life expectancy is not less than 12 weeks. at least one measurable lesion according to RECIST 1.1. Absolute neutrophil count (ANC) ≥ 1.5×10^9/L, Platelets ≥90×10^9/L, Hemoglobin ≥ 90 g/L; Total bilirubin≤1.5 upper limit of normal (ULN)；Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST)≤2.5×ULN (ALT and AST≤5×ULN if liver metastasis); blood urea nitrogen (BUN) and Creatinine (Cr)≤1.5×ULN Left ventricular ejection fraction (LVEF) ≥ 50% and QTc≤470 ms Exclusion Criteria: Patients who received Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine kinase inhibitors (TKI); II: Patients who received fulvestrant, everolimus or cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor; Ib: Patients who had symptomatic brain metastasis; II: Patients who had brain metastasis; Patients unsuitable for endocrine therapy; Unable to swallow, chronic diarrhea and intestinal obstruction, there are many factors affecting drug use and absorption. Participated in other drug clinical trials within 4 weeks before admission Other malignant tumors, excluding cured cervical carcinoma in situ, skin basal cell carcinoma or skin squamous cell carcinoma, have been diagnosed in the past five years. Active human immunodeficiency virus (HIV), hepatitis B or hepatitis C; Has suffered from any heart disease Female patients during pregnancy and lactation, fertile women with positive baseline pregnancy tests or women of childbearing age who are unwilling to take effective contraceptive measures throughout the trial According to the judgement of the researchers, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of research (including, but not limited to, severe hypertension, severe diabetes, active infections, etc.). Moderate infection occurs within 4 weeks before the first administration (e.g. intravenous drip of antibiotics, antifungal or antiviral drugs according to clinical criteria), fever（> 38.5 ℃） of unknown origin occurs during the screening period/before the first administration. Researchers believe that patients are unsuitable for any other situation in this study.

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: Treatment group<br>Famitinib Plus SHR6390 and Endocrine therapy | Drug: Famitinib<br>* Famitinib orally, daily or every other day<br>Drug: SHR6390<br>* SHR6390 orally, daily for 3 weeks followed by 1 week off<br>* Other names: Dalpiciclib;Drug: Fulvestrant<br>* Fulvestrant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RP2D in phase Ib | Recommended phase II dose (PR2D) in phase Ib | Up to 4 weeks | 
| ORR in phase II | Objective response rate (ORR) by investigator in phase II | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR in phase Ib | ORR by investigator in phase Ib | up to 2 years | 
| PFS in phase Ib | Progression-Free Survival (PFS) in phase Ib | up to 2 years | 
| PFS in phase II | Progression-Free Survival in phase II | up to 2 years | 
| AE | The number of patients experiencing any adverse events (AE) during the phase II study time | up to 2 years |