A Single-arm, Prospective Phase Ⅱ Clinical Study of Utidelone Combined with Capecitabine in the Treatment of Active Brain Metastasis of TNBC

A Single-arm, Prospective Phase Ⅱ Clinical Study of Utidelone Combined with Capecitabine in the Treatment of Active Brain Metastasis of Triple-negative Advanced Breast Cancer.

This study aims to explore the efficacy and safety of the combination therapy of utidelone and capecitabine in the treatment of brain metastases from triple-negative advanced breast cancer, and to search for systemic treatment for brain metastases from triple-negative advanced breast cancer cases.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Utidelone and capecitabine

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Min Yan, Doctor; Phone Number: +8615713857388; Email: ym200678@126.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University
      • Contact: Min Yan, Doctor; Phone Number: +86 15713857388; Email: ym200678@126.com
      • Contact: Min Yan, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years old;
2. Invasive breast cancer confirmed by histological or cytological examination, accompanied by metastatic disease; Patients with metastatic diseases not confirmed by pathology or cytology should obtain clear evidence of metastasis through physical examination or radiological research;
3. Based on the pathological report of recent biopsy or other pathological specimens (confirmed by the laboratory of the participating research center), the histology and/or cytology are confirmed as triple negative breast cancer. The specific requirements include: a) the definition of negative human epidermal growth factor receptor 2(HER2): the immunohistochemistry (IHC) is 0 or 1+; If IHC was 2+, it was confirmed negative by fluorescence in situ hybridization (FISH). B) Negative estrogen and progesterone receptors means that IHC examination shows ER < 10% and or PR < 10%, and the researcher evaluates that patients cannot benefit from endocrine therapy.
4. Newly diagnosed brain metastases or brain metastases that have progressed after local treatment: patients with brain metastases who met all the criteria of this scheme before starting from September 1, 2023 and did not meet all the exclusion criteria can also be included;
5. Patients must have measurable central nervous system diseases, defined as at least one brain parenchymal lesion, which can be accurately measured in at least one dimension through local radiological examination; And there is no central nervous system symptom or symptom controllable, so radiotherapy is not needed urgently.
6. Patients who have previously received at least one taxane and/or one anthracycline antibiotic (as a treatment history of neoadjuvant therapy, adjuvant therapy or metastatic therapy or both);
7. Allow (new) adjuvant therapy to have recurrence and metastasis after stopping using Utterone and/or Capecitabine for more than one year, or stop taking drugs for non-progressive reasons in the rescue stage;
8. The physical status score (ECOGPS) of the eastern cancer cooperative group is 0-2, and the life expectancy is more than 12 weeks;
9. Normal organ and bone marrow function; Blood routine examination was basically normal within one week before joining the group (based on the normal laboratory of each research center): neutrophil count (ANC) ≥ 1.5× 109/L; Hemoglobin (HB) ≥ 90g/L; Platelet count (PLT) ≥ 75× 109/L; Liver and kidney function tests were basically normal within one week before enrollment (based on the normal values of laboratories in each research center): total bilirubin (TBIL)≤1.5× upper limit of normal value (ULN); Alanine aminotransferase (SGPT/ALT)≤2.5×ULN (patients with liver metastasis ≤ 5 XULN); Aspartate aminotransferase (SGOT/AST)≤2.5× upper limit of normal value (ULN); Creatinine clearance rate (Ccr)≥60ml/min.
10. Neuropathy should be < grade 2 within 4 weeks before enrollment (version 5.0 of ncictcae);
11. No major organ dysfunction and no heart disease;
12. Women and male patients with reproductive potential must agree to use appropriate contraceptive measures before the start of the study and during the study participation.

Exclusion Criteria:

1. Patients with extensive meningeal metastasis and brain metastasis who are ineffective in dehydration treatment with hormones or in urgent need of radiotherapy;
2. Invasive breast cancer confirmed by histological or cytological examination, accompanied by metastatic disease; Patients with metastatic diseases not confirmed by pathology or cytology should obtain clear evidence of metastasis through physical examination or radiological research;
3. Received chemotherapy, major surgery, targeted therapy or immunotherapy within 2 weeks before joining the group (the interval between targeted therapy and immunotherapy is at least 2 weeks or at least 5 half-lives, whichever is shorter); Received endocrine therapy within 1 week before joining the group; He had received nitrosourea or mitomycin chemotherapy within 6 weeks before joining the group;
4. Receive unlisted clinical trial drugs within 4 weeks before entering the group;
5. Previous history of grade 3 or 4 allergic reactions related to Utterone or Capecitabine;
6. inability to swallow, chronic diarrhea and intestinal obstruction, there are many factors that affect the taking and absorption of drugs;
7. Known contraindications for gadolinium MRI contrast agents, such as pacemakers, shrapnel or ocular foreign bodies;
8. Suffering from other malignant tumors in the past 3 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of skin, squamous cell carcinoma of skin or early thyroid carcinoma;
9. Seizures occurred more than 2 times within 4 weeks before joining the group;
10. Poor control of hypertension; Or have a history of hypertensive crisis or hypertensive encephalopathy;
11. Have a history of bleeding in the central nervous system of grade 3 or above within 12 months;
12. Suffering from serious or uncontrollable diseases, including but not limited to: 1) active virus infection, such as HIV and HBV active phase (HbsAg positive and HBV-DNA≥103, hepatitis C antibody positive); 2) Suffering from severe cardiovascular disease in the past: uncontrollable hypertension; Myocardial infarction, unstable arrhythmia, congestive heart failure, pericarditis, myocarditis, etc. According to NYHA criteria, patients with grade Ⅲ ~ Ⅳ cardiac insufficiency, or those with left ventricular ejection fraction (LVEF) less than 50% indicated by echocardiography; 12. Suffering from serious or uncontrollable diseases, including but not limited to: 1) active virus infection, such as HIV and HBV active phase (HbsAg positive and HBV-DNA≥103, hepatitis C antibody positive); 2) Suffering from severe cardiovascular disease in the past: uncontrollable hypertension; Myocardial infarction, unstable arrhythmia, congestive heart failure, pericarditis, myocarditis, etc. According to NYHA criteria, patients with grade Ⅲ ~ Ⅳ cardiac insufficiency, or those with left ventricular ejection fraction (LVEF) less than 50% indicated by echocardiography;
13. Have a history of hemoptysis within 6 months before joining the group; Or evidence of bleeding tendency or obvious coagulation dysfunction in the last month;
14. Currently receiving full-dose warfarin or equivalent drugs, or taking aspirin (325mg/ day) within 10 days; 15.28 days or in the course of the study, it is expected that major surgery, open biopsy or major trauma are needed;

16. Those who have a history of abdominal fistula or gastrointestinal perforation in the first 6 months; There are unhealed wounds, active ulcers or untreated fractures; Pregnant or lactating women; 17. Those who have a history of psychotropic substance abuse and cannot quit or patients with mental disorders; 18. According to the judgment of the researcher, there are other patients with accompanying diseases that seriously endanger the safety of patients or affect the completion of the study; 19. Those who are known to have allergic history to the drug components of this scheme; Have a history of immunodeficiency, including HIV positive, HCV or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 20. The history of live attenuated vaccine inoculation within 28 days before the first study or the person who is expected to be vaccinated with live attenuated vaccine in the study; 21. Any situation that the researcher thinks is not suitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: One arm involving utidelone and capecitabine; Combination use of utidelone and capecitabine Utidelone 30 mg/m2 d1-5(single-day dose allowed ± 10% fluctuation) , once every three weeks; capecitabine: 1000 mg/m2, twice daily, orally after meal (one in the morning and one in the evening, with an interval of about 12 hours, equivalent to a daily dose of 2000 mg/m2) ; The drug was administered consecutively on days 1-14, with a 21-day cycle.

Drug: Utidelone and capecitabine; Utidelone: intravenous capecitabine: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CNS-ORR（RANO Standard）	CNS-ORR（RANO Standard）	From the date of enrollment to the date of first documented progression or death from any cause, whichever comes first，assessed up to 48 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CNS-ORR (RECIST1.1 standard)	CNS-ORR (RECIST1.1 standard)	From the date of enrollment to the date of first documented progression or death from any cause, whichever comes first，assessed up to 48 months.
CNS-PFS assessed by the investigator	CNS-PFS assessed by the investigator	From the date of enrollment to the date of first documented progression or death from any cause, whichever comes first，assessed up to 48 months.

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Principal Investigator: Min Yan, Doctor, Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: September 13, 2024
• First Posted (Estimated): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 13, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: HNCH-MBC15-BM06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No