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

NCT ID: NCT06539559

Last Updated: 2024-08-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-01
• Study Completion Date: 2026-08-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

eribulin+bevacizumab

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

Group Type: EXPERIMENTAL

Eribulin

Intervention Type: DRUG

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

Bevacizumab

Intervention Type: 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.

eribulin

eribulin 1.4 mg/m2 iv d1,8/q21d

Group Type: ACTIVE_COMPARATOR

Eribulin

Intervention Type: DRUG

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

Interventions

Eribulin

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

Intervention Type: DRUG

Bevacizumab

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.

Intervention Type: DRUG

Other Intervention Names

Halaven; Avastin

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years old，and ≤75 years old.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

3. Expected survival period not less than 12 weeks.

4. At least 1 measurable lesion according to RECIST 1.1 standard.

5. previously treated with taxanes and/or anthracycline drugs in any stage of breast cancer.

6. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) validated HER2 negative, including IHC- and IHC 1+/2+ with FISH negative.

7. at least prior 1 line of chemotherapy in the advanced stage.

8. 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；
• BUN and Cr≤1.5×ULN and the Creatinine Clearance Rate ≥50 mL/min (Cockcroft-Gault formula calculated)；

(3). Echocardiogram

• LVEF≥50%；

(4). electrocardiogram

• The QT interval (QTcF) corrected by Fridericia method less than 450 ms for male and less than 470 ms for female.

9. Volunteer to join this study, sign informed consent, have good compliance and be willing to cooperate with follow-up.

Exclusion Criteria

1. 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).

2. Symptomatic or uncontrolled brain or meningeal metastases.

3. Patients with only bone or skin metastasis as the assessable lesion.

4. Previously suffered from other malignant tumors.

5. Those who have used Eribulin during the advanced disease stage.

6. 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.

7. Any heart disease or other conditions evaluated unsuitable by the researcher.

8. 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.

9. 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.).

10. Having a clear history of neurological or mental disorders, including epilepsy or dementia.

11. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Wang Jiayu

OTHER

Sponsor Role: lead

Responsible Party

Wang Jiayu

Chief Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jiayu Wang, doctor

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Locations

Beijing Chaoyang District San Huan Cancer Hospital

Beijing, Beijing Municipality, China

Cancer Hospital of HuanXing ChaoYang District

Beijing, Beijing Municipality, China

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Countries

China

Central Contacts

Yan Wang, doctor

Role: CONTACT

wangyan07425@163.com

+86-15600990767

Hangcheng Xu, doctor

Role: CONTACT

xuhangcheng15@126.com

+86-19800353631

References

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Other Identifiers

CancerIHCAMS-Wjiayu

Identifier Type: -

Identifier Source: org_study_id