Trial Title:
Efficacy and Safety of Disitamab Vedotin Plus Pyrotinib or Naratinib in HER2-positive Breast Cancer Patients With Brain Metastasis
NCT ID:
NCT06015113
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Brain Neoplasms
Disitamab vedotin
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Disitamab Vedotin plus pyrotinib or naratinib
Description:
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.
Arm group label:
Label 1
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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Xi'an International Medical Center Hospital
Address:
City:
Xi'an
Zip:
710100
Country:
China
Contact:
Last name:
Yan Xue
Phone:
0086-13992830596
Email:
1410605462@qq.com
Start date:
September 2023
Completion date:
April 2027
Lead sponsor:
Agency:
Xi'an International Medical Center Hospital
Agency class:
Other
Source:
Xi'an International Medical Center Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06015113
