Efficacy and Safety of Disitamab Vedotin Plus Pyrotinib or Naratinib in HER2-positive Breast Cancer Patients With Brain Metastasis

NCT06015113 | Not Yet Recruiting

• 1 other identifier: ECCO-KY-22004
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Basis: Brain metastasis is very common in breast cancer, and HER2 positivity is a risk factor for high incidence of brain metastasis, with approximately 50% of HER2+ MBC cases experiencing brain metastasis. The reason for this is that as the efficacy of HER2-targeted therapy improves, the survival of these patients significantly extends, leading to an increase in the occurrence rate of brain metastasis events in the late stage of MBC. In the systemic treatment of HER2+ breast cancer brain metastasis, various HER2-targeted drugs have been explored, but none have achieved satisfactory therapeutic effects. Therefore, it is imperative to explore new treatment options. ADC drugs have shown some efficacy in brain metastasis patients, and as a domestically developed ADC drug, trastuzumab vedotin has demonstrated good anti-tumor effects. The treatment model combining trastuzumab vedotin with small molecule TKIs has been rarely reported, so we are attempting to use the treatment model of trastuzumab vedotin combined with pyrotinib or neratinib to explore its efficacy and safety in patients with HER2-positive brain metastasis. Method: The plan is to recruit HER2-positive breast cancer patients with brain metastasis and use the treatment of trastuzumab vedotin combined with pyrotinib or neratinib (specific treatment drugs to be selected during the study). Procedure: All subjects will undergo screening, treatment, and follow-up periods, strictly adhering to relevant GCP regulations during the treatment process. Expectations: Through this study, preliminary efficacy and safety data of trastuzumab vedotin combined with pyrotinib or neratinib treatment will be provided for patients with HER2+ brain metastatic BC.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  It is an indicator of the long-term efficacy of the drug.

  The time from randomization to the first documented tumor progression or death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (3)

• Objective Response Rate

  4 weeks

• Disease Control Rate

  4 weeks

• Overall survival

  the time from randomization to death from any cause，whichever came first, assessed up to 100 months.

Study Arms (1)

Label 1

EXPERIMENTAL

tale Disitamab Vedotin with pyrotinib or neratinib

Drug: Disitamab Vedotin plus pyrotinib or naratinib

Interventions

Disitamab Vedotin plus pyrotinib or naratinib DRUG

Trastuzumab Injection: Intravenous infusion, initial loading dose of 2 mg/kg, administered via intravenous infusion over 30-90 minutes (usually recommended around 60 minutes), administered on day 1 of each cycle, with each cycle lasting 14 days. Pyrotinib Maleate Tablets: 400 mg, taken orally once daily, within 30 minutes after a meal, at the same time every day. Taken continuously, with each cycle lasting 14 days. Neratinib Maleate Tablets: 240 mg, taken orally once daily with a meal, at the same time every day. The neratinib tablet should be swallowed whole (it should not be chewed, crushed, or split before swallowing). Taken continuously, with each cycle lasting 14 days.

Label 1

Eligibility Criteria

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

You may qualify if:

• Patients who can voluntarily sign an informed consent form;
• Females aged ≥18 years old when signing the informed consent form;
• ECOG PS physical status score of 0 to 2 points;
• Histologically confirmed HER2-positive metastatic breast cancer patients; Note: HER2 positivity refers to at least one occurrence of tumor cell immunohistochemical staining intensity of 3+ or confirmed as positive by fluorescence in situ hybridization \[FISH\] in the pathological testing/re-review of the primary or metastatic lesions conducted by the participating center's pathology department;
• Brain metastases confirmed by MRI/enhanced CT, with at least one measurable lesion in the brain based on RECIST 1.1 criteria;
• Expected survival period ≥3 months;
• Patient types: Cohort A - newly diagnosed brain metastases patients; Cohort B - patients with progression after whole-brain radiotherapy or stereotactic radiosurgery;
• Left ventricular ejection fraction (LVEF) ≥50%;
• QT interval corrected by Fridericia formula (QTcF) of 12-lead electrocardiogram: \<450ms for males, \<470ms for females;
• The following conditions should be met in the blood routine examination:① Absolute neutrophil count (ANC) ≥1.5×10\^9/L, ② Platelet count ≥100×10\^9/L, ③ Hemoglobin ≥90g/L, ④ White blood cell count ≥3.0×10\^9/L;
• Liver function meets the following conditions: ① Serum total bilirubin ≤1.5×upper limit of normal (ULN), or ≤3×ULN if there are liver metastases, ② Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3×ULN, or ≤5×ULN if there are liver metastases;
• Renal function meets the following conditions: Serum creatinine ≤1.5×ULN or creatinine clearance ≥50mL/min (calculated according to the Cockroft-Gault formula);
• Female patients who meet the following conditions can participate in this study: ① Infertility; ② Capable of fertility, with a negative blood pregnancy test result within 7 days before the first administration of the investigational drug, not breastfeeding, and adopting effective contraceptive measures during the screening period, throughout the study, and within 6 months after the last administration of the study drug.

You may not qualify if:

• Patients who have received treatment with anti-HER2 ADC drugs;
• Patients who have received sequential treatment with pyrotinib and neratinib;
• Patients with extensive leptomeningeal metastases and poor response to steroid dehydration therapy for brain metastases;
• Presence of third space fluid accumulation (such as significant pleural effusion or ascites) that cannot be controlled by drainage or other methods;
• Patients who have received chemotherapy, major surgery, or molecular targeted therapy within 2 weeks prior to enrollment; patients who have received endocrine therapy within 1 week prior to enrollment; patients who have received nitrosoureas or mitomycin chemotherapy within 6 weeks prior to enrollment;
• Concurrent use of any other anticancer treatment;
• History of or current concurrent malignancies within the past 5 years, excluding cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder carcinoma \[Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading the lamina propria)\];
• Underwent major surgery (including thoracotomy biopsy), experienced significant trauma (such as fractures), had unhealed wounds or fractures at the time of screening, or anticipated the need for major surgery during the study treatment period, within the 4 weeks prior to randomization;
• History of myocardial infarction within the past 6 months; history of New York Heart Association (NYHA) class ≥II congestive heart failure that is not controlled by medication, severe arrhythmias that cannot be controlled (excluding atrial fibrillation and paroxysmal supraventricular tachycardia); known decrease in LVEF to below 50% during or after previous treatment with trastuzumab;
• Known allergy to the drugs and excipients involved in this trial;
• Known history of hypersensitivity reactions to any investigational drugs;
• Subjects deemed unsuitable for participation by other investigators.

Sponsors & Collaborators

• Xi'an International Medical Center Hospital: lead

Study Sites (1)

Xi'an International Medical Center Hospital

Xi'an, Shaanxi, 710100, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

disitamab vedotin; pyrotinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Yan Xue

  Xi'an International Medical Center Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yan Xue

CONTACT

0086-13992830596; 1410605462@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of tumor hospital

Study Record Dates

• First Submitted: August 8, 2023
• First Posted: August 29, 2023
• Study Start: September 1, 2023
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: August 29, 2023

Record last verified: 2023-08

Locations

CN (1)