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

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 Overview

• Status: Not yet recruiting
• Conditions: Advanced Breast Cancer; Treatment; HR Low/HER2 Negative
• Intervention / Treatment: Drug: Experimental: chemotheyapy; Drug: Active Comparator: endocrine therapy

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 Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Min Yan, M.D.; Phone Number: +8615713857388; Email: ym200678@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; nab-paclitaxel 130mg/m2，day 1 and day 8 Capecitabine 2000mg/m2，from day1 to DAY 14 Vinorelbine 25mg/m2，day 1 and day 8	Drug: Experimental: chemotheyapy; nab-paclitaxel 130mg/m2，day 1 and day 8 + Capecitabine 2000mg/m2, followed by nab-paclitaxel 130mg/m2，day 1 and day 8 or Capecitabine from day1 to DAY 14 Vinorelbine 25mg/m2，day 1 and day 8 + Capecitabine 2000mg/m2，from day1 to DAY 14; Other Names: Vinorelbine 25mg/m2，day 1 and day 8 + Capecitabine 2000mg/m2，from day1 to DAY 14
Active Comparator: B; palbociclib/Dalpiciclib Letrozole/Anastrozole/fulvestrant	Drug: Active Comparator: endocrine therapy; palbociclib 125mg per day for 21days Dalpiciclib 150mg per day for 21days Letrozole 2.5mg per day Anastrozole 1mg per day fulvestrant 500mg per 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR by investigator using RECIST Guideline (Version 1.1)	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	6 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 20, 2023
• Primary Completion (Estimated): December 20, 2025
• Study Completion (Estimated): December 20, 2026

Study Registration Dates

• First Submitted: December 9, 2023
• First Submitted That Met QC Criteria: December 9, 2023
• First Posted (Actual): December 19, 2023

Study Record Updates

• Last Update Posted (Actual): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 9, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Capecitabine; Vinorelbine
• Other Study ID Numbers: HNCH-MBC013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No