H (Trastuzumab or Biosimilar) Combined With CDK4/6 Inhibitor + AI±OFS in the Treatment of HR+HER2+ Advanced Breast Cancer Efficacy and Safety: a Chinese Multi-center Real World Study

Exploratory Study of HR-positive HER2-positive MBC Combined Treatment Plan

This study is a multi-center prospective real-world clinical study, mainly evaluating the efficacy and safety of H combined with CDK4/6 inhibitor + AI in the treatment of HR+/HER2+ advanced breast cancer; exploring potential biomarkers.

Study Overview

• Status: Recruiting
• Conditions: Advanced HR+ HER2 Negative Breast Carcinoma
• Intervention / Treatment: Drug: Enituzumab injection+Abesili tablets+Anastrozole tablets

Detailed Description

This study is a multi-center, prospective. Because of the non-interventional nature of this study, the choice of H can be trastuzumab, biosimilar drugs Hantriyou, enituzumab, etc. The CDK4/6 inhibitor can be piperazil, abecilil and the like. AI can be letrozole, anastrozole, exemestane. This study does not change or interfere with clinicians' diagnosis and treatment decisions, as well as patients' actual medical practices.This real-world study will not do formal inference statistical analysis. All hypothesis testing is exploratory. A comprehensive statistical analysis plan (SAP) will be prepared and finalized before the data is locked and analyzed. Descriptive statistics will be performed, including the number and percentage of categorical variables, as well as the number, average, standard deviation, median, maximum, and minimum of continuous variables. Kaplan-Meier survival analysis was used to calculate the median PFS and OS and their 95% confidence intervals. The median time to disease progression and median survival time will also be calculated, as well as its 95% confidence interval. ORR and CBR will be analyzed and expressed by the ratio and the corresponding 95% confidence interval (CI). The multivariate logistic regression model was used to calculate the odds ratio (OR) and its 95% confidence interval and p-value. The subgroup analysis of PFS and OS was analyzed by Log-rank test. The COX proportional hazard regression model is used to calculate the hazard ratio and its 95% confidence interval.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chunfang Hao, PhD; Phone Number: 13602031629; Email: haochf@163.com

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Tianjin Cancer Hospital
    • Contact: Chunfang Hao, PhD; Phone Number: 13602031629; Email: haochf@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years old.

2. HR-positive and HER2-positive breast cancer diagnosed pathologically.

   1. ER positive and/or PR positive is defined as: the proportion of positively stained tumor cells in all tumor cells is ≥10% (reviewed and confirmed by the investigator at the test center);
   2. HER2 positive is defined as: standard immunohistochemistry (IHC) test for HER2 (3+), or HER2 (2+), FISH test is positive (reviewed and confirmed by the investigator at the test center).
3. After H-based combined chemotherapy treatment has progressed (≤1 line), or the combined treatment is effective but not suitable for continued combined chemotherapy; or initially unsuitable for targeted combined chemotherapy for recurrent metastatic breast cancer or inoperable locally advanced breast cancer Breast cancer patients.
4. Postmenopausal or premenopausal/perimenopausal female patients can be included in the group. Premenopausal or perimenopausal female patients must be willing to receive LHRHa treatment during the study period.
5. According to the RECIST 1.1 standard, patients can have: a) measurable lesions; b) without measurable lesions, unmeasurable osteolytic or mixed (osteolytic + osteogenic) bone lesions. c) Unmeasurable lesions.

6. The main organs are functioning normally, that is, they meet the following standards:

   1. The standard of routine blood examination should meet:

      Hb≥80 g/L; ANC≥1.5×109 /L; PLT≥75×109 /L;

   2. The biochemical inspection shall meet the following standards:

      TBIL≤1.5×ULN (upper limit of normal value); ALT and AST≤2.5×ULN; if there is liver metastasis, ALT and AST≤5×ULN; Serum creatinine ≤1.5×ULN, creatinine clearance ≥50ml/min (based on Cockroft and Gault formula);

   3. Heart color Doppler ultrasound Left ventricular ejection fraction (LVEF) ≥50%.

Exclusion Criteria:

1. Patients who have previously received CDK4/6 inhibitor drug therapy.
2. T-DM1 treats patients.
3. Female patients during pregnancy or lactation.
4. Suffer from serious concomitant diseases, such as infectious diseases; there are many factors that affect the oral and absorption of drugs.
5. Patients considered by the investigator to be unsuitable to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Trastuzumab injection+Piperacillil tablets+Letrozole tablets; Trastuzumab injection:Once in 21 days IVD；Piperacillil tablets:125mg qd (d1-21) PO；Letrozole tablets:2.5mg POqd；According to the current clinical guidelines combined with clinical practice, the treating physicians recommended the treatment plan to the subjects, and decided to enroll HR+/HER2+ advanced breast cancer patients treated with H combined with CDK4/6 inhibitor + AI±OFS into this study

Drug: Enituzumab injection+Abesili tablets+Anastrozole tablets; According to the current clinical guidelines combined with clinical practice, the treating physicians recommended the treatment plan to the subjects, and decided to enroll HR+/HER2+ advanced breast cancer patients treated with H combined with CDK4/6 inhibitor + AI±OFS into this study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	From enrollment to progression or death (for any reason)	Estimated 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Ratio of CR and PR in all subjects	Estimated 24 months
Disease Control Rate (DCR)	Ratio of CR ,PR and SD in all subjects	Estimated 24 months
Overall survival (OS)	From enrollment to death (for any reason)	Estimated 36 months
Security (CTCAE 5.0)	Adverse events are described in terms of CTCAE 5.0	From informed consent through 28 days following treatment completion

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Investigators: Principal Investigator: Chunfang Hao, PhD, Department of Breast Cancer Medical Oncology

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2022
• Primary Completion (Anticipated): October 23, 2022
• Study Completion (Anticipated): August 23, 2024

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Anastrozole
• Other Study ID Numbers: BC-CIH-H-RWS

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