A Study of SHR6390 Combined With Famitinib in the Treatment of ER + / HER2- Advanced Breast Cancer

Study Overview
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Brief Summary
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The study is being conducted to assess the safety 、tolerability 、 pharmacokinetics and efficacy of SHR6390 combined with famitinib in the treatment of ER + / HER2- advanced breast cancer.

Official Title
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A Phase I Study to Evaluate Safety 、Tolerability 、 Pharmacokinetics and Efficacy of SHR6390 in Combination With Famitinib in the Treatment of ER + / HER2- Advanced Breast Cancer

Conditions
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ER+ / HER2- Advanced Breast Cancer

Intervention / Treatment
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* Drug: SHR6390、Famitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects aged 18 to 75 years old； ECOG performance status 0-1; Life expectancy is not less than 12 weeks; Histological or cytological confirmation of ER+/HER2- recurrent/metastatic breast cancer; Participants with measurable disease must have at least one target lesion to be used to assess response on this protocol as defined by RECIST1.1; Adequate function of major organs; Voluntary participation in the study, signed informed consent, good compliance and willingness to cooperate with follow-up. Exclusion Criteria: Confirmed diagnosis of HER2 positive disease; Participants who previously received SHR6390 or VEGFR inhibitors; Allergy to study drug or its components; Participated in other drug clinical trials within 4 weeks before the first dose; Other malignancies within 3 years, except cured non-melanoma skin cancer , skin basal cell carcinoma and squamous-cell carcinoma or carcinoma in situ of the cervix; 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； Tumor has invaded important blood vessels or the tumor is likely to invade important blood vessels and cause fatal hemorrhage during treatment; Urine routine test indicates urine protein ≥(++), or 24-hour urine protein >1.0g; Active HBV/HCV/HIV infection; The investigators determined that other conditions were inappropriate for participation in this clinical trial； Pregnant or breast-feeding women; Central nervous system (CNS) invasion.

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: SHR6390+famitinib<br>Participants will receive SHR6390 in combination with famitinib. | Drug: SHR6390、Famitinib<br>* SHR6390, oral;Famitinib, oral.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Safety Lead-in) dose limited toxicity (DLT) of SHR6390+famitinib in the first cycle |  | up to 28 days | 
| (Safety Lead-in) Recommended Phase II Dose (RP2D) of SHR6390+famitinib |  | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs+SAEs | from the first drug administration to within 30 days for the last treatment dose | up to 24 months | 
| Evaluation of pharmacokinetic parameter of SHR6390+famitinib: Cmax |  | 6 months | 
| Evaluation of pharmacokinetic parameter of SHR6390+famitinib: Tmax |  | 6 months | 
| Evaluation of pharmacokinetic parameter of SHR6390+famitinib: t1/2 |  | 6 months | 
| Evaluation of pharmacokinetic parameter of SHR6390+famitinib: AUC |  | 6 months | 
| Evaluation of pharmacokinetic parameter of SHR6390+famitinib: CL/F |  | 6 months | 
| Evaluation of pharmacokinetic parameter of SHR6390+famitinib: Vz/F |  | 6 months | 
| Evaluation of pharmacokinetic parameter of SHR6390+famitinib: Rac |  | 6 months | 
| Objective Response Rate (ORR) | Number of responders Assessed by Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1) for target lesions assessed by CT or MRI | up to 24 months | 
| Disease control rate (DCR) | Complete response + Partial response + Stable disease (CR+PR+SD) based on RECIST 1.1 | up to 24 months | 
| Duration of response (DoR) | Time from documentation of tumor response to disease progression assessed among patients who had an objective response | up to 24 months |