Efficacy and Resistant Mechanism of Eribulin and Bevacizumab for Advanced HER2 Negative Breast Cancer
NCT Number: NCT06539559
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Breast Neoplasms|Neoplasm Metastasis|Drug Therapy|Bevacizumab
Interventions: DRUG: Eribulin|DRUG: Bevacizumab
Sponsor: Wang Jiayu
Collaborators: Chinese Academy of Medical Sciences
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08-01
Completion Date: 2026-08-01
Locations: Beijing Chaoyang District San Huan Cancer Hospital, Beijing, Beijing, 100021, China|Cancer Hospital of HuanXing ChaoYang District, Beijing, Beijing, 100021, China|Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, Beijing, 100021, China

Summary:
This study is a prospective, multicenter, phase II randomized clinical trial. It is planned to enroll 60 patients with advanced HER2 negative breast cancer, who will be randomly assigned to the experimental group and the control group in a 1:1 ratio. The participants will receive either eribulin combined with bevacizumab or eribulin monotherapy. Every treatment cycle will last for 21 days, with weekly monitoring of blood routine, blood biochemistry and other indicators. Imaging examinations will be conducted every two cycles and the efficacy will be evaluated according to RECIST 1.1 standard. The life quality questionnaire is arranged at baseline and every 3 months after enrollment, and the long-time survival will be followed every 3 months after treatment. The primary endpoint is progression-free survival (PFS), the secondary endpoints are objective response rate (ORR), clinical benefit rate (CBR) and overall survival (OS). The investigators will also focus on the treatment-related adverse events (TRAE) and quality of life (QoL) assessment.

At the same time, this study also aims to explore the resistant mechanisms of anti-angiogenic drugs. The investigators plan to collect peripheral venous blood samples at 3 time points: baseline, during treatment, and end of treatment. All the dynamic samples will be used for transcriptome sequencing to obtain the gene sets. And based on the optimal therapeutic efficacy, all the participants will be divided into response group and non-response group. GO and KEGG enrichment analysis will be subsequently performed between different therapeutic efficacy groups to draw gene interaction networks, identify key action nodes and explain the mechanism of anti-angiogenic drug resistance.

Primary Outcome Measures: progression-free survival (PFS), PFS is defined as the time from randomization to the date of confirmed radiological progression or death from any cause., Radiological examinations will be conducted every two cycles: at the end of Cycle 2, 4, 6, 8......(each cycle is 21 days). The PFS will last until disease progression.
Secondary Outcome Measures: overall survival (OS), OS is defined as the time from randomization to the date of death from any cause and censored at the date of final contact for patients who were still alive., The long-time survival will be followed every 3 months after the end of treatment.|objective response rate (ORR), ORR is defined as the proportion of patients with best response of complete response (CR) and partial response (PR) according to RECIST 1.1 standard., Radiological examinations will be conducted every two cycles: at the end of Cycle 2, 4, 6, 8......(each cycle is 21 days). The efficacy will be evaluated according to RECIST 1.1 standard.|clinical benefit rate (CBR), CBR is defined as the proportion of patients with best response of complete response (CR) , partial response (PR) and stable disease (SD) according to RECIST 1.1 standard., Radiological examinations will be conducted every two cycles and the efficacy will be evaluated according to RECIST 1.1 standard.
Other Outcome Measures: treatment-related adverse events (TRAE), TRAE is defined as the adverse reactions that occur during the use of medication for treatment and are supposed to be related to the intervention drugs., Adverse events will be assessed every cycle (each cycle is 21 days) and graded according to the Common Terminology Criteria Adverse Events (CTCAE) version 5 until 1 month after the end of treatment.|quality of life (QoL), QoL assessment is examined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30), of which 30 items were included. Items 1-28 are divided into 4 levels, with ratings ranging from 1 to 4 (the higher score indicates worse life quality). Items 29 and 30 are divided into 7 levels, with ratings ranging from 1 to 7 (the higher score indicates better life quality)., The life quality questionnaire is arranged at baseline and every 3 months after enrollment until 6 months after the end of treatment.