Apatinib Combined With cdk4/6i in First-line Treatment for HR+/HER2- SNF4 Subtype Breast Cancer

Phase 3

Recruiting

• Conditions: HR+/HER2- Breast Cancer; Advanced Breast Cancer
• Interventions: Drug: Apatinib; Drug: CDK4/6 Inhibitor; Drug: Aromatase inhibitor and Fulvestrant

• Registration Number: NCT06447623
• Lead Sponsor: Fudan University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-01
• Status Verified: 2024-06
• Study First Submitted: 2024-06-03
• Study First Submitted QC: 2024-06-03
• Last Update Submitted: 2024-06-03
• Study First Posted: 2024-06-07
• Last Update Posted: 2024-06-07
• Primary Completion: 2027-02-01
• Study Completion: 2029-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 184

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:

    1. Blood routine examination standards should meet: HB≥90g/L (no blood transfusion within 14 days); ANC≥1.5×109/L; PLT≥75×109/L;
    2. Biochemical examination shall meet the following standards: TBIL≤1.5×ULN (upper limit of normal value); ALT and AST≤3 x ULN; In case of liver metastasis, ALT and AST≤5×ULN; Serum Cr ≤1.5×ULN, endogenous creatinine clearance > 50ml/min (Cockcroft-Gault formula);

  • 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

  • Patients with central nervous system metastasis out of control (symptoms need to use glucocorticoids or mannitol).
  • A history of clinically significant or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction within the last 6 months, or ventricular arrhythmia;
  • Radiotherapy, chemotherapy, surgery, other targeted therapy, and immunotherapy for advanced HR+/HER2- breast cancer within 4 weeks before the first administration of drugs used in this study.
  • Pregnant or lactating patients;
  • Other malignancies within the previous 3 years, excluding cured skin basal cell carcinoma and cervical carcinoma in situ;
  • Significant comorbid medical conditions, including mental illnesses that the investigator or sponsor believes would adversely affect the patient's participation in the study;
  • Allergic physique, or known allergic history of the drug components of this program; Or allergic to other monoclonal antibodies;
  • The investigator does not consider the patient suitable for participation in any other circumstances of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm-A	CDK4/6 Inhibitor	Apatinib combined with cdk4/6i and Endocrine therapy.
Arm-B	Aromatase inhibitor and Fulvestrant	cdk4/6i and Endocrine therapy.
Arm-A	Aromatase inhibitor and Fulvestrant	Apatinib combined with cdk4/6i and Endocrine therapy.
Arm-A	Apatinib	Apatinib combined with cdk4/6i and Endocrine therapy.
Arm-B	CDK4/6 Inhibitor	cdk4/6i and Endocrine therapy.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Approximately 5 years	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.

Secondary Outcome Measures

Name	Time	Method
Clinical Benefit Rate (CBR)	Approximately 5 years	CBR is the total percentage of participants who achieved a complete response, partial response, or had stable disease for 6 months or more.
Objective Response Rate (ORR)	Approximately 5 years	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.
Overall Survival (OS)	Approximately 5 years	OS is defined as the time from randomisation until the date of death due to any cause.
Safety and tolerability	Approximately 5 years	Number of adverse events according to NCI-CTCAE Version 5.0 per each treatment arm.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China