Breast CancerNCT06015113
Efficacy and Safety of Disitamab Vedotin Plus Pyrotinib or Naratinib in HER2-positive Breast Cancer Patients With Brain Metastasis
A study testing Disitamab Vedotin plus pyrotinib or naratinib in people with Breast Cancer, run by Xi'an International Medical Center Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Disitamab Vedotin plus pyrotinib or naratinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Sep 2023to Apr 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Xi'an International Medical Center Hospital
Xi'an, Shaanxi, 710100
Yan Xue, 0086-13992830596, 1410605462@qq.com
About this study
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).
Read more
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.
Read the detailed description
Treatment Plan After patient screening, patients will receive treatment with trastuzumab injection plus either pyrotinib maleate tablets or neratinib maleate tablets, with each cycle lasting 14 days until disease progression. 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. If a patient misses a dose of pyrotinib, it should not be made up for, and the next dose should be taken as scheduled. 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. If a patient misses a dose of neratinib, it should not be made up for, and the next dose should be taken as scheduled. Note: The choice between pyrotinib maleate tablets or neratinib maleate tablets for treatment should be based on the patient's previous treatment history as decided by the investigator. Treatment medication should be continued until disease progression or the occurrence of intolerable toxic reactions.
Study Steps 1) Screening Period (Visit 1: -14 to -1 days, approximately 2 weeks): Subjects will sign an informed consent form during Visit 1 and undergo a series of examinations (see Table 1. Treatment Flowchart). Based on the examination results and inclusion/exclusion criteria, the investigator will determine if the subject meets the inclusion criteria and does not meet the exclusion criteria. 2) Treatment Period (Visit 2 to disease progression, 1 visit every 2 cycles): Subjects will receive treatment with trastuzumab injection plus pyrotinib maleate tablets plus capecitabine tablets on the experimental Day 0, with each cycle lasting 21 days, until disease progression. During this period, a series of examinations will be conducted every 2 cycles (see flowchart for visits 2 to N). The investigator will evaluate the effectiveness and safety of the treatment based on the subject's examination results. 3) Survival Follow-up Period (1 follow-up every 3 months after withdrawal from the study): After patients withdraw due to disease progression or other endpoint events, a telephone follow-up will be conducted every 3 months until the patient's death or loss to follow-up. Detailed records of disease progression, related treatments, and survival information should be documented.
- Conditions
- Breast Cancer
- Being tested
- Disitamab Vedotin plus pyrotinib or naratinib
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Disitamab Vedotin plus pyrotinib or naratinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Label 1 | Experimental | tale Disitamab Vedotin with pyrotinib or neratinib Receives: Drug: Disitamab Vedotin plus pyrotinib or naratinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
It is an indicator of the long-term efficacy of the drug.
Measured: 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
The proportion of patients with the best response of complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST).
Measured: 4 weeks
Disease Control Rate
The proportion of patients with tumor shrinkage or stability maintained for a certain period, including cases of CR, PR, and stable disease (SD)
Measured: 4 weeks
Overall survival
It is an indicator of the long-term efficacy of the drug.
Measured: the time from randomization to death from any cause，whichever came first, assessed up to 100 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2023
- Study startSep 2023 (estimated)
- Primary completionApr 2026 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xi'an International Medical Center Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yan Xue, Xi'an International Medical Center Hospital
- Investigators
- Yan Xue, Principal investigator, Xi'an International Medical Center Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06015113
- Sponsor's protocol ID
- ECCO-KY-22004
- Status last verified
- Aug 2023
- First submitted
- 8 Aug 2023
- Last updated
- 29 Aug 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Disitamab Vedotin Plus Pyrotinib or Naratinib in HER2-positive Breast Cancer Patients With Brain Metastasis
- ClinicalTrials.gov ID
- NCT06015113
- Acronym / sponsor ID
- ECCO-KY-22004
- Conditions
- Breast Cancer
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Xi'an International Medical Center HospitalUniversity, hospital or other
- Study start
- Sep 2023 (estimated)
- Primary completion
- Apr 2026 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 29 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Treatment Plan After patient screening, patients will receive treatment with trastuzumab injection plus either pyrotinib maleate tablets or neratinib maleate tablets, with each cycle lasting 14 days until disease progression. 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. If a patient misses a dose of pyrotinib, it should not be made up for, and the next dose should be taken as scheduled. 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. If a patient misses a dose of neratinib, it should not be made up for, and the next dose should be taken as scheduled. Note: The choice between pyrotinib maleate tablets or neratinib maleate tablets for treatment should be based on the patient's previous treatment history as decided by the investigator. Treatment medication should be continued until disease progression or the occurrence of intolerable toxic reactions.
Study Steps 1) Screening Period (Visit 1: -14 to -1 days, approximately 2 weeks): Subjects will sign an informed consent form during Visit 1 and undergo a series of examinations (see Table 1. Treatment Flowchart). Based on the examination results and inclusion/exclusion criteria, the investigator will determine if the subject meets the inclusion criteria and does not meet the exclusion criteria. 2) Treatment Period (Visit 2 to disease progression, 1 visit every 2 cycles): Subjects will receive treatment with trastuzumab injection plus pyrotinib maleate tablets plus capecitabine tablets on the experimental Day 0, with each cycle lasting 21 days, until disease progression. During this period, a series of examinations will be conducted every 2 cycles (see flowchart for visits 2 to N). The investigator will evaluate the effectiveness and safety of the treatment based on the subject's examination results. 3) Survival Follow-up Period (1 follow-up every 3 months after withdrawal from the study): After patients withdraw due to disease progression or other endpoint events, a telephone follow-up will be conducted every 3 months until the patient's death or loss to follow-up. Detailed records of disease progression, related treatments, and survival information should be documented.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Label 1 | Experimental | Drug: Disitamab Vedotin plus pyrotinib or naratinibtale Disitamab Vedotin with pyrotinib or neratinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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;
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Disitamab Vedotin plus pyrotinib or naratinibTrastuzumab 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. | Drug | Label 1 |
Primary outcome
Progression-free survival
Time frame: The time from randomization to the first documented tumor progression or death from any cause, whichever came first, assessed up to 100 months
It is an indicator of the long-term efficacy of the drug.
3 secondary outcomes
Objective Response Rate
Time frame: 4 weeks
Disease Control Rate
Time frame: 4 weeks
Overall survival
Time frame: the time from randomization to death from any cause，whichever came first, assessed up to 100 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yan Xue principal investigator
Xi'an International Medical Center Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Disitamab Vedotin plus pyrotinib or naratinib in people with Breast Cancer, run by Xi'an International Medical Center Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 29 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yan Xue (0086-13992830596, 1410605462@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: The time from randomization to the first documented tumor progression or death from any cause, whichever came first, assessed up to 100 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2023.