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This is a randomized, controlled, open-label, phase III study to explore the efficacy and safety of Apatinib in combination with standard first-line endocrine therapy for the HR+/ HER2-SNF4 subtype of advanced breast cancer. The study was used to explore the efficacy of Apatinib in combination with standard endocrine therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm-A | Experimental | Apatinib combined with cdk4/6i and Endocrine therapy. |
|
| Arm-B | Active Comparator | cdk4/6i and Endocrine therapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Apatinib | Drug | Apatinib is a kind of TKI inhibitor. |
| |
| CDK4/6 Inhibitor |
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) | The interval from randomization until the first occurrence of disease progression (according to RECIST 1.1) or death from any cause, which ever occurs first. | Approximately 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Benefit Rate (CBR) | CBR is the total percentage of participants who achieved a complete response, partial response, or had stable disease for 6 months or more. | Approximately 5 years |
| Objective Response Rate (ORR) |
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Inclusion Criteria:
Inclusion Criteria:
Patients need to meet all of the following conditions
Patients must be ≥18 and ≤ 75 years of age;
Pathologically confirmed breast cancer is HR+/HER2- breast cancer (IHC ER >10%, or/and PR>10%, HER 0 OR +, if HER2++, FISH negative);
SNF4 subtype definition: SNF4 subtype confirmed by digital pathology of H&E sections;
Locally advanced breast cancer (radical local therapy is not possible) or metastatic breast cancer (without using adjuvant CDK4/6 inhibitors in the past, or one year after adjuvant CDK4/6 inhibitor therapy has ended);
No prior therapy (chemotherapy, targeted therapy, etc.) for advanced or metastatic breast cancer;
Patients with at least one measurable lesion that has not previously received radiation therapy and can be evaluated repeatedly according to RECIST 1.1;
The functions of the main organs are basically normal, and the following conditions are met:
ECOG performance status 0 or 1; The expected survival is more than 3 months;
Fertile female is required to use a medically approved contraceptive during study treatment and for at least 3 months after the last use of the study drug;
Patients voluntarily join the study, sign the informed consent, have good compliance, and cooperate with follow-up.
Exclusion Criteria:
Patients with any of the following conditions were excluded from the study
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhimin Shao, MD, PhD | Contact | 86-021-64175590 | 88807 | zhimingshao@yahoo.com |
| Peng Ji, MD | Contact | 86-021-64175590 | 62978 | JIPENG_1010@163.COM |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Recruiting | Shanghai | Shanghai Municipality | 200032 | China |
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| ID | Term |
|---|---|
| C553458 | apatinib |
| D047072 | Aromatase Inhibitors |
| D000077267 | Fulvestrant |
| ID | Term |
|---|---|
| D065088 | Steroid Synthesis Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
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| Drug |
Dalpiciclib (SHR6390) is a kind of CDK4/6 inhibitor that has demonstrated tolerability and preliminary clinical activity in patients with heavily pretreated hormone receptor-positive, HER2-negative advanced breast cancer. |
|
| Aromatase inhibitor and Fulvestrant | Drug | Endocrine therapy combined with CDK4/6 inhibitors is the standard first-line therapy for advanced luminal breast cancer. Investigators choose endocrine therapy including Letrozole, Anastrozole, Exemestane, and Fulvestrant. Postmenopausal participants should use Goserelin. |
|
ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR) based on BICR and investigator assessment using RECIST 1.1.
| Approximately 5 years |
| Overall Survival (OS) | OS is defined as the time from randomisation until the date of death due to any cause. | Approximately 5 years |
| Safety and tolerability | Number of adverse events according to NCI-CTCAE Version 5.0 per each treatment arm. | Approximately 5 years |
| D020164 | Chemical Actions and Uses |
| D004965 | Estrogen Antagonists |
| D006727 | Hormone Antagonists |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D004958 | Estradiol |
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |