Pyrotinib Combined With Capecitabine and Bevacizumab for Patients With HER2 Positive Breast Cancer and Brain Metastases

Pyrotinib Combined With Capecitabine and Bevacizumab for Patients With HER2 Positive Breast Cancer and Brain Metastases：a Single-arm,Prospective,Phase II Study

This study intends to conduct a small, prospective, single-center clinical study to explore and evaluate the efficacy and safety of pyrrotinib combined with capecitabine and bevacizumab in HER2-positive advanced breast cancer with brain metastases.The overall objective is to provide a new drug regimen for HER2 positive breast cancer patients with brain metastases by balancing survival benefits and patient quality of life.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer With Brain Metastases
• Intervention / Treatment: Drug: pyrotinib+capecitabine+bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chao tengfei; Phone Number: 02783663409; Email: turnface@126.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Tongji Hospital Affiliated of Tongji Medical College Huazhong University of Science and Technology
      • Contact: Chao tengfei; Phone Number: 02783663409; Email: turnface@126.com
      • Principal Investigator: Chao tengfei

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years old
2. ECOG PS score ≤2
3. Pathologically confirmed advanced breast cancer with positive HER-2 expression;
4. Patients with brain metastases identified by MRI/ enhanced CT with at least one measurable lesion of brain parenchyma according to RECIST 1.1 criteria. There are no requirements as to whether extracranial lesions can be measured.
5. Patients with brain metastases who have not received local treatment in the past and have been treated more than two weeks since the end of the last systemic treatment。Patients with new brain lesions after craniotomy were allowed if they did not receive postoperative radiotherapy and were at least 2 weeks away from surgery.

6. Previous treatment:

   1. Prior treatment with trastuzumab and other HER2-targeting macromolecular antibodies is permitted;
   2. Prior chemotherapy was allowed with any line of chemotherapy. Prior use of endocrine therapy is permitted
   3. Patients who had not previously used capecitabine or progressed after 6 months of discontinuation during metastatic disease or 12 months of discontinuation during adjuvant therapy were admitted.
   4. Concomitant use of bisphosphonates, mannitol, and glucocorticoids was allowed, provided that the glucocorticoid dose was stable for at least a week before enrollment and that the hormone dose was less than 5mg/ day of dexamethasone or equivalent.
7. The expected survival is not less than 6 months.

8. Major organ function is normal, meet the following criteria:

   1. Blood routine: ANC ≥1.0×109/L;PLT ≥100×109/L;Hb ≥90g/L
   2. Blood biochemistry: TBIL ≤1.5 times the upper limit of normal (ULN); ALT and AST≤3 times ULN;For patients with liver metastases, ALT and AST≤5×ULN; BUN and Cr≤1×ULN and creatinine clearance ≥50mL/min (CockcroftGault formula);
   3. Heart color ultrasound: LVEF≥50%;
   4. 12-lead electrocardiogram: Fridericia corrected QT interval (QTcF) < 450ms for males and < 470 ms for females.
9. Voluntarily participate in this study, sign informed consent, have good compliance and be willing to cooperate with follow-up.

Exclusion Criteria:

1. Patients with known leptomeningeal metastases, defined as positive imaging or CSF cytology, or clear indications of clinically significant leptomeningeal involvement.
2. need emergency neurosurgery intervention (e.g., removal, shunt placement) of CNS complications.Patients with brain metastases that are poorly controlled by hormonal dehydration and hormonal therapy, such as uncontrollable intracranial hypertension, ejection vomiting, mental disorders, epilepsy, cognitive impairment, etc.
3. There is a third space effusion that cannot be controlled by drainage or other methods (such as excessive pleural fluid and ascites).
4. Patients who had received chemotherapy, surgery or molecular targeted therapy within 2 weeks before enrollment; Patients who received endocrine therapy within 1 week prior to enrollment; Minor procedures such as tumor biopsy, thoracopuncture, or intravenous catheter placement are permitted.
5. Participated in other new drug clinical trials within 4 weeks before enrollment.
6. Have used or currently using tyrosine kinase inhibitors targeting HER-2 (including lapatinib, lenatinib and pyrrotinib, etc.).
7. Other malignancies within the previous 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma, or skin squamous cell carcinoma.
8. Receive any other anti-tumor therapy.
9. Have used or currently using bevacizumab

10. There are other concurrent serious and/or uncontrolled conditions that may affect the study, including any of the following:

    1. unable to swallow, chronic diarrhoea and intestinal obstruction, with multiple factors affecting drug use and absorption;
    2. patients with allergy or known history of allergy to the components of this regimen; A history of immunodeficiency, including HIV testing positive, or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation;
    3. had serious heart disease, including: a.myocardial infarction; b. Heart failure; c.any other heart disease that the investigator determines is not suitable for participation in the study;
    4. infection;
11. Pregnant and lactating women, fertile women who tested positive for baseline pregnancy tests, or women of childbearing age who were unwilling to use effective contraception throughout the trial period.
12. The investigator considers the patient unsuitable for participation in any other circumstances of the 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: treatment group; pyrotinib+capecitabine+bevacizumab	Drug: pyrotinib+capecitabine+bevacizumab; pyrotinib: ≥160mg qd capecitabine: 1000mg/m2,bid,q1-14,q3w bevacizumab:7.5mg/kg,iv,q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate in the CNS	Assess the response rate in the CNS by MRI according to modified Response Assessment in modified RECIST 1.1 criteria. Objective CNS response is defined as at least 30% decrease in the sum of diameters of CNS target lesions in the absence of new lesions (defined as ≥ 6 mm), increased steroid use, progressive neurological symptoms, and progressive extra-CNS disease as assessed by RECIST 1.1. Confirmatory scans are not required.	Up to 2 years
Time to CNS progression	Time to CNS progression will be defined as the time from treatment initiation to documented disease progression (modified RECIST 1.1 criteria) in the CNS	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	OS is defined as the time from treatment initiation until death due to any cause	Up to 3 years
Progression Free Survival	PFS is defined as the time from treatment initiation to documented disease progression	Up to 2 years
Overall Response Rate	Evaluate systemic ORR defined as partial response or complete response assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to 2 years
Safety	Refers to the proportion of patients with a clinically significant adverse event (AE) (ie, leading to treatment modification or discontinuation, patient hospitalization, death, or permanent sequelae) documented in the medical records.	up to 2 years

Collaborators and Investigators

• Sponsor: Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 30, 2023
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: November 22, 2023
• First Submitted That Met QC Criteria: November 22, 2023
• First Posted (Estimated): December 1, 2023

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 22, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: capecitabine; breast cancer; bevacizumab; brain metastases; pyrotinib
• 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; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Bevacizumab
• Other Study ID Numbers: TJ-IRB20230957

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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