Utidelone Plus Bevacizumab for Advanced Breast Cancer With Brain Metastases

Utidelone Plus Bevacizumab for Advanced Breast Cancer With Brain Metastases: A Multicenter, Single Arm, Open Label, Phase II Trial

This study aims to investigate the efficacy and safety of utidelone in combination with bevacizumab in the treatment of advanced breast cancer with brain metastases, and thus provides a new systemic treatment strategy for those patients.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: utidelone; Drug: Bevacizumab

Detailed Description

This is a multicenter,open label, phase 2 trial to investigate the efficacy and safety of utidelone in combination with bevacizumab in the treatment of advanced breast cancer with brain metastases. Patients with HER2-negative advanced breast cancer who have received at least one prior anthracycline and one prior taxane or HER2-positive advanced breast cancer who have failed trastuzumab and pyrotinib, and with at least one measurable CNS lesion are eligible for the study.

This study includes 2 cohorts, and the Simon two-stage design are applied, respectively. A total of 48 patients with HER2-negative advanced breast cancer are included in cohort 1, and 52 patients with HER-2 positive patients are enrolled in cohort 2. Patients in both cohorts receive bevacizumab, 15mg/kg, day 1, and utidelone, 30mg/m2 (±10%), day 1-5 every 3-week cycle until disease progression or unmanageable toxicity. The primary endpoint is CNS-ORR according to the RECIST 1.1. The secondary endpoints include CNS-ORR according to RANO criteria, CNS-PFS assessed by investigator, extracranial ORR, extracranial PFS, OS, time to WBRT, quality of life and safety profile according to NCI-CTCAE 5.0.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Huimin Lv; Email: lvhuimin999@163.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Min Yan, Professor; Phone Number: +86 15713857388; Email: ym200678@126.com
      • Principal Investigator: Min Yan, Professor

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Aged ≥ 18 years; histologically or cytologically confirmed invasive breast cancer with metastatic disease; patients without pathologically or cytologically confirmed metastatic disease must have physical or radiological proof of metastasis;
2. With measurable CNS disease, defined as at least one parenchymal brain lesion that can be accurately measured in at least one dimension by local radiology;
3. Previously treated with at least one anthracycline and one taxane (as neoadjuvant therapy, adjuvant therapy, palliative therapy, or both);
4. Patients in cohort 2 have failed trastuzumab and pyrotinib treatment;
5. Prior unproven treatment progression with utidelone or bevacizumab;
6. ECOG PS of 0-1 and life expectancy exceeding 12 weeks;
7. Normal organ and bone marrow function; normal blood sample within one week before enrollment (as determined by the laboratory's normal values in each center), including WBC ≥ 3.0 x 109/L, ANC ≥ 1.5×109/L, PLT ≥ 100×109/L; normal kidney and liver function within one week before enrollment (as determined by the laboratory's normal values in each center), including TBIL ≤ 1.5 ULN, SGPT/ALT ≤ 2.5 ULN (≤ 5 ULN in patients with liver metastases), SGOT/AST ≤ 2.5 ULN, Ccr ≥ 60 ml/min;
8. Neurological lesions must be < grade 2 according to NCI CTCAE version 5.0 within four weeks before enrollment;
9. Without major organ dysfunction or heart disease;
10. Those of childbearing potential should use appropriate contraception before and during study period.

Exclusion Criteria:

1. Patients with leptomeningeal metastases who are not adequately treated by dehydration, hormone therapy, or urgently need radiotherapy;
2. Presence of effusions that cannot be controlled by drainage or other treatment (e.g., massive pericardial, thoracic, or abdominal effusions);
3. Patients received WBRT, chemotherapy, major surgery, targeted therapy or immunotherapy within two weeks before enrollment, received endocrine therapy within one week before enrollment, or received nitrosourea or mitomycin based chemotherapy within six weeks before enrollment；
4. Participation in another clinical trial within four weeks before enrollment；
5. History of grade 3 or 4 allergic events to bevacizumab or utidelone;
6. Contraindications to MRI gadolinium-based contrast agents, such as pacemakers, shrapnel or intraocular foreign bodies;
7. Other malignancies within three years, except for cured cervical carcinoma in situ, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma;
8. More than two seizures within four weeks before enrollment;
9. Insufficiently controlled hypertension, or history of hypertensive crisis or hypertensive encephalopathy;
10. CNS hemorrhage of grade 2 or higher within 12 months before enrollment;
11. NYHA class II or severe congestive heart failure, or history of myocardial infarction or unstable angina within six months;
12. History of hemoptysis within six months before enrollment, or evidence of bleeding tendency or significant coagulation dysfunction within one month;
13. Receiving full dose of warfarin or equivalent currently, or using aspirin (325 mg/day) within ten days;
14. Needs for major surgery, open biopsy or with major trauma within 28 days or during the study period;
15. History of abdominal fistula or gastrointestinal perforation within six months；
16. Presence of unhealed wound, active ulcer or untreated fracture;
17. Any other condition inappropriate for this study deemed by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cohort 1; HER2-negative advanced breast cancer with brain metastases who have received at least one prior anthracycline and one prior taxane	Drug: utidelone; 30mg/m2 (±10%), day 1-5 every 3-week cycle; Drug: Bevacizumab; 15mg/kg, day 1
Experimental: cohort 2; HER2-positive advanced breast cancer with brain metastases who have failed trastuzumab and pyrotinib	Drug: utidelone; 30mg/m2 (±10%), day 1-5 every 3-week cycle; Drug: Bevacizumab; 15mg/kg, day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CNS-ORR according to the RECIST 1.1.	the proportion of patients with the best intracranial response of confirmed complete or partial response according to RECIST 1·1, as assessed by the investigator	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CNS-ORR according to RANO criteria	the proportion of patients with the best intracranial response of confirmed complete or partial response according to RANO criteria, as assessed by the investigator	up to 2 years
CNS-PFS assessed by investigator	time from the first dose to disease progression or any-cause death	up to 2 years
extracranial ORR	proportion of patients with confirmed extracranial complete or partial response per RECIST 1·1	up to 2 years
extracranial PFS	time from the first dose to disease progression or any-cause death	up to 2 years
OS	time from the first dose of study drug to any-cause death	Estimated up to 3 year

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2022
• Primary Completion (Anticipated): May 1, 2024
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: April 21, 2022
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): May 2, 2022

Study Record Updates

• Last Update Posted (Actual): September 16, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: brain metastases;bevacizumab;utidelone
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: HNCH-MBC08-BM02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after de-identification are available following article publication.
• IPD Sharing Time Frame: Three years from publication
• IPD Sharing Access Criteria: Please contact Central contact person by Email
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No