Combination Followed by Maintenance Chemotherapy Versus CDK4/6 Inhibitor Combined With Endocrine Therapy for HR Low/HER2-negative Advanced Breast Cancer: a Prospective, Randomized, Open-label Phase Ⅱ Clinical Trial

Phase 2

Recruiting

• Conditions: HR Low/HER2 Negative; Treatment; Advanced Breast Cancer

• Registration Number: NCT06176534
• Lead Sponsor: Henan Cancer Hospital

Brief Summary

To observe the differences in the efficacy of Combination followed by maintenance chemotherapy versus CDK4/6 inhibitor combined with endocrine therapy in HR low expression /HER2 negative advanced breast cancer, and to provide new evidence for the best treatment of HR low expression /HER2 negative advanced breast cancer, and to explore the efficacy and safety of combined/maintenance chemotherapy.

Detailed Description

To observe the differences in the efficacy of Combination followed by maintenance chemotherapy versus CDK4/6 inhibitor combined with endocrine therapy in HR low expression /HER2 negative advanced breast cancer, and to provide new evidence for the best treatment of HR low expression /HER2 negative advanced breast cancer, and to explore the efficacy and safety of combined/maintenance chemotherapy.

Study Timeline

• Study First Submitted: 2023-12-09
• Study First Submitted QC: 2023-12-09
• Study First Posted: 2023-12-19
• Study Start: 2024-01-01
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-20
• Primary Completion: 2025-12-20
• Study Completion: 2026-12-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

1. age ≥18 years old; Invasive breast cancer with metastatic disease confirmed by histological or cytological examination; Patients without pathologically or cytologically confirmed metastatic disease should have clear evidence of metastasis by physical examination or radiological studies;

2. The most recent pathological report of biopsy confirmed HR low expression and HER2 negative.

   1. HR low expression was defined as 1-50% ER expression by immunohistochemistry (IHC); Or ER<1% and PR≥1%; Patients with ER expression of 1-10% or ER-/ PR-positive patients were eligible for inclusion after careful evaluation by the investigator, and those with a small tumor burden and candidates for endocrine therapy were eligible.
   2. HER2-negative definition: IHC 0 or 1+; If the IHC was 2+, it was confirmed negative by fluorescence in situ hybridization (FISH).

3. at least one measurable lesion;

4. No previous salvage chemotherapy for metastatic disease was required, and first-line endocrine therapy was allowed;

5. no previous CDK4/6 inhibitor; For adjuvant CDK4/6i treatment, recurrence and metastasis were required more than 1 year after drug withdrawal.

6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, life expectancy is more than 12 weeks;

7. Adequate function of major organs.

8. All adverse events recovered to grade 1 or less before enrollment (NCI CTCAE version 5.0);

9. patients without major organ dysfunction and heart disease;

10. Women and men of childbearing potential must agree to use appropriate contraception before and during study participation.

Exclusion Criteria

1. symptomatic, uncontrolled brain or leptomeningeal metastases; Patients who had received previous systemic radical treatment for brain metastases (radiotherapy or surgery), if stable disease had been maintained for at least 1 month as confirmed by imaging, and if systemic hormone therapy (dose 10mg/ day prednisone or other effective hormones) for more than 2 weeks without clinical symptoms.
2. patients received radiotherapy, chemotherapy, major surgery, targeted therapy or immunotherapy within 2 weeks before enrollment; Patients received endocrine therapy within 1 week before enrollment. Chemotherapy with nitrosourea or mitomycin was administered within 6 weeks before enrollment.
3. participated in other clinical trials of new drugs within 4 weeks before enrollment;
4. there can not be controlled by drainage or pneumatic methods third space effusion;
5. patients with other malignant tumors within the past 3 years, excluding radical cervical carcinoma in situ, skin basal cell carcinoma or skin squamous cell carcinoma;
6. suffering from serious or uncontrolled diseases, including but not limited to: 1) active viral infection, such as HIV or HBV active (HbsAg positive and HBV-DNA≥103, hepatitis C antibody positive); 2) history of severe cardiovascular disease: uncontrolled hypertension; Myocardial infarction, unstable arrhythmia, congestive heart failure, pericarditis, myocarditis, etc. Patients with NYHA class ⅲ-ⅳ cardiac dysfunction, or left ventricular ejection fraction (LVEF) 50% by echocardiography; 3) severe infection (e.g., intravenous antibiotic, antifungal, or antiviral therapy according to clinical practice) within 4 weeks prior to the first dose or unexplained fever during screening/before the first dose; 38.3°C (fever due to cancer, as judged by the investigator, was eligible);
7. patients with a history of psychotropic drug abuse and unable to abstain or with mental disorders; Or accompanied by swallowing and absorption dysfunction;
8. patients with other concomitant diseases that seriously endanger the safety of patients or affect the completion of the study according to the judgment of the investigators;
9. patients with known history of allergy to the components of this regimen; A history of immunodeficiency, including testing positive for HIV, HCV or other acquired or congenital immunodeficiency disorders, or a history of organ transplantation;
10. pregnant or lactating women;
11. Patients deemed unsuitable for inclusion by the investigators.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
ORR by investigator using RECIST Guideline (Version 1.1)	6 weeks	ORR was defined as percentage of participants with best (confirmed) overall response (BOR) of either CR or PR assessed by the investigator according to RECIST version 1.1

Secondary Outcome Measures

Name	Time	Method
Adverse events	up to 1.5 years	Proportion of participants experienced adverse events during the study period
PFS	up to 1.5 years	PFS was defined as the time from first dose to first documented disease progression (PD) or death from any cause, whichever occurred first
OS	up to 3 years	OS was defined as the time from first dose to death for any cause

Trial Locations

Locations (1)

Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China