Efficacy and Resistant Mechanism of Eribulin and Bevacizumab for Advanced HER2 Negative Breast Cancer

NCT06539559 | Not Yet Recruiting Phase 2

• 1 other identifier: CancerIHCAMS-Wjiayu
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Breast Neoplasms; Neoplasm Metastasis; Drug Therapy; Bevacizumab

Keywords

breast cancer; HER2 negative; eribulin; bevacizumab; efficacy; resistant mechanism

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• overall survival (OS)

  The long-time survival will be followed every 3 months after the end of treatment.

• objective response rate (ORR)

  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)

  Radiological examinations will be conducted every two cycles and the efficacy will be evaluated according to RECIST 1.1 standard.

Other Outcomes (2)

• treatment-related adverse events (TRAE)

  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)

  The life quality questionnaire is arranged at baseline and every 3 months after enrollment until 6 months after the end of treatment.

Study Arms (2)

eribulin+bevacizumab

EXPERIMENTAL

eribulin 1.4 mg/m2 iv d1,8 + bevacizumab 7.5mg/kg ivgtt d1/q21d

Drug: Eribulin; Drug: Bevacizumab

eribulin

ACTIVE COMPARATOR

eribulin 1.4 mg/m2 iv d1,8/q21d

Drug: Eribulin

Interventions

Eribulin DRUG

Based on the results of STUDY301 and STUDY304, eribulin showed outstanding therapeutic effect and tolerable adverse events in patients with metastatic breast cancer

Also known as: Halaven

eribulin; eribulin+bevacizumab

Bevacizumab DRUG

Study E2100, AVADO and RIBBON-1 found that in the first-line chemotherapy for advanced breast cancer, the addition of bevacizumab can significantly improve the efficacy of traditional chemotherapy drugs. Study RIBBON-2 and TANIA have confirmed the effectiveness of bevacizumab in the second and third line treatment of advanced HER2 negative breast cancer. Compared with chemotherapy alone, the addition of bevacizumab can prolong the PFS by 0.6 to 2.1 months.

Also known as: Avastin

eribulin+bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old，and ≤75 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Expected survival period not less than 12 weeks.
• At least 1 measurable lesion according to RECIST 1.1 standard.
• previously treated with taxanes and/or anthracycline drugs in any stage of breast cancer.
• Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) validated HER2 negative, including IHC- and IHC 1+/2+ with FISH negative.
• at least prior 1 line of chemotherapy in the advanced stage.
• The organ function must meet the following requirements：
• (1). Blood Routine
• ANC≥1.5×109/L；
• PLT≥90×109/L；
• Hb≥90 g/L；
• (2). Blood Biochemistry
• TBIL≤1.5×ULN；
• ALT and AST≤2×ULN；ALT和AST≤5×ULN for patients with liver metastasis；

You may not qualify if:

• There is a third interstitial fluid accumulation that cannot be controlled by drainage or other methods (such as a large amount of hydrothorax and ascites).
• Symptomatic or uncontrolled brain or meningeal metastases.
• Patients with only bone or skin metastasis as the assessable lesion.
• Previously suffered from other malignant tumors.
• Those who have used Eribulin during the advanced disease stage.
• Individuals with a known history of allergies to the components of the interventions; History of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases and a history of organ transplantation.
• Any heart disease or other conditions evaluated unsuitable by the researcher.
• Pregnant and lactating female patients, female patients with fertility and positive baseline pregnancy test results, or female patients of reproductive age who are unwilling to take effective contraceptive measures throughout the trial period.
• According to the investigator's judgment, there are concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study (including severe bleeding tendency, history of surgery within 2 weeks, hypertension beyond drug control, serious diabetes, active infection, thyroid disease, etc.).
• Having a clear history of neurological or mental disorders, including epilepsy or dementia.
• According to the RECIST 1.1 criteria, researchers determined that patients who received the last anti-tumor regimen before enrollment did not experience disease progression.

Sponsors & Collaborators

• Wang Jiayu: lead
• Chinese Academy of Medical Sciences: collaborator

Study Sites (3)

Beijing Chaoyang District San Huan Cancer Hospital

Beijing, Beijing Municipality, 100021, China

Location

Cancer Hospital of HuanXing ChaoYang District

Beijing, Beijing Municipality, 100021, China

Location

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

Related Publications (8)

• Hardy-Bessard AC, Brocard F, Clatot F, Lortholary A, You B, Grenier J, Martin-Babau J, Lucas B, Meunier J, Ferrero JM, Savoye AM, Marti A, Despax R, Moullet I, Emile G. First-line bevacizumab and eribulin combination therapy for HER2-negative metastatic breast cancer: Efficacy and safety in the GINECO phase II ESMERALDA study. Breast. 2020 Dec;54:256-263. doi: 10.1016/j.breast.2020.09.011. Epub 2020 Sep 30.

  PMID: 33188992 BACKGROUND

• Yuan P, Hu X, Sun T, Li W, Zhang Q, Cui S, Cheng Y, Ouyang Q, Wang X, Chen Z, Hiraiwa M, Saito K, Funasaka S, Xu B. Eribulin mesilate versus vinorelbine in women with locally recurrent or metastatic breast cancer: A randomised clinical trial. Eur J Cancer. 2019 May;112:57-65. doi: 10.1016/j.ejca.2019.02.002. Epub 2019 Mar 29.

  PMID: 30928806 BACKGROUND

• Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20;33(6):594-601. doi: 10.1200/JCO.2013.52.4892. Epub 2015 Jan 20.

  PMID: 25605862 BACKGROUND

• Liu B, Liu L, Ran J, Xie N, Li J, Xiao H, Yang X, Tian C, Wu H, Lu J, Gao J, Hu X, Cao M, Shui Z, Hu ZY, Ouyang Q. A randomized trial of eribulin monotherapy versus eribulin plus anlotinib in patients with locally recurrent or metastatic breast cancer. ESMO Open. 2023 Jun;8(3):101563. doi: 10.1016/j.esmoop.2023.101563. Epub 2023 Jun 6.

  PMID: 37285718 BACKGROUND

• von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. doi: 10.1016/S1470-2045(14)70439-5. Epub 2014 Sep 28.

  PMID: 25273342 BACKGROUND

• Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. doi: 10.1200/JCO.2010.34.1255. Epub 2011 Oct 11.

  PMID: 21990397 BACKGROUND

• Robert NJ, Dieras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. doi: 10.1200/JCO.2010.28.0982. Epub 2011 Mar 7.

  PMID: 21383283 BACKGROUND

• De Angelis C, Bruzzese D, Bernardo A, Baldini E, Leo L, Fabi A, Gamucci T, De Placido P, Poggio F, Russo S, Forestieri V, Lauria R, De Santo I, Michelotti A, Del Mastro L, De Laurentiis M, Giuliano M, De Placido S, Arpino G. Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI). ESMO Open. 2021 Apr;6(2):100054. doi: 10.1016/j.esmoop.2021.100054. Epub 2021 Feb 16.

  PMID: 33601296 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

eribulin; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jiayu Wang, doctor

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yan Wang, doctor

CONTACT

+86-15600990767; wangyan07425@163.com

Hangcheng Xu, doctor

CONTACT

+86-19800353631; xuhangcheng15@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: July 28, 2024
• First Posted: August 6, 2024
• Study Start: August 1, 2024
• Primary Completion: February 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: August 6, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After the final analysis of this study on August 2026.

Locations

CN (3)