Clinical trial NCT05167643: 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
Official title: Exploratory Study of HR-positive HER2-positive MBC Combined Treatment Plan
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Advanced HR+ HER2 Negative Breast Carcinoma
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2021-12-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Estimated 24 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Estimated 24 months
measure: Disease Control Rate (DCR)
timeFrame: Estimated 24 months
measure: Overall survival (OS)
timeFrame: Estimated 36 months
measure: Security (CTCAE 5.0)
timeFrame: From informed consent through 28 days following treatment completion
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
Study officials:
affiliation: Department of Breast Cancer Medical Oncology
name: Chunfang Hao, PhD
role: PRINCIPAL_INVESTIGATOR
References: