Trial Title:
Neratinib Tablets Monotherapy for Advanced Solid Tumors With HER2 Mutations
NCT ID:
NCT06519110
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Neratinib
Conditions: Keywords:
HER2 mutation-positive
Non-Small Cell Lung Cancer (NSCLC)
Cholangiocarcinoma
Cervical Cancer
Salivary Gland Cancer
Neratinib tablets
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Patients with advanced solid tumors (non-small cell lung cancer, cholangiocarcinoma,
cervical cancer, salivary gland cancer) with HER2 mutations.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Neratinib tablets
Description:
In the first week, take Neratinib tablets 120mg orally, in the second week take Neratinib
tablets 160mg orally, and from the third week until the end of treatment, take Nilotinib
tablets 240mg orally (from Cycle 1 Day 15 until the end of treatment).
Arm group label:
(Trial group)-Neratinib tablets
Other name:
Neratinib
Summary:
Evaluating the efficacy of Neratinib tablets monotherapy in treating advanced solid
tumors with HER2 mutations.
Detailed description:
This single-arm, open-label, multicenter Phase II clinical study is divided into three
phases: screening, treatment, and follow-up. The screening phase occurs within 28 days
prior to the first administration of the study drug. During the treatment phase, a 28-day
cycle is used, and tumor efficacy is assessed according to the RECIST 1.1 criteria.
Assessments are conducted at the end of the first cycle (±3 days), followed by imaging
evaluations every 8 weeks until disease progression. During the treatment period, the
investigator may increase the number of assessments based on clinical needs. The study
drug will be administered continuously until intolerable adverse reactions occur, disease
progression, withdrawal of informed consent, loss to follow-up, death, or study
termination.
The follow-up phase includes safety and survival follow-up. Safety follow-up occurs
within 28 days after the last administration of the study drug. Survival follow-up is
conducted every 12 weeks to collect the survival status of the subjects until their
death, loss to follow-up, withdrawal from the study, or study termination (whichever
occurs first).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 1.Age is 18 years or older, and the patient can be male or female;
- 2.Histologically or cytologically confirmed advanced non-small cell lung cancer,
cholangiocarcinoma, cervical cancer, and salivary gland cancer patients; those who
have failed to respond to ≤2 lines of standard treatment (disease progression after
treatment or intolerable toxic side effects of treatment), or have no standard
treatment options, or are unable to receive standard treatment;
- 3.Previously underwent second-generation sequencing testing with evidence of HER2
mutation, otherwise, the patient must provide sufficient tissue samples for
second-generation sequencing testing in the study's central laboratory, with tissue
samples being the primary source; if tissue slices or samples that meet the
requirements cannot be obtained, blood samples may be provided for testing.
- 4.According to the RECIST v1.1 criteria (see Appendix 1), there must be at least one
measurable lesion; if the only lesion is one that has previously received local
treatment (such as radiotherapy, ablation, interventional treatment, etc.), there
must be clear radiological evidence of disease progression;
- 5.Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1;
- 6.Predicted survival is 3 months or more;
- 7.Bone marrow reserve must meet the following laboratory value criteria: Absolute
neutrophil count (ANC) is ≥1.5 × 10^9/L; Platelet count (PLT) is ≥90 × 10^9/L;
Hemoglobin (Hb) is ≥90 g/L; Aspartate aminotransferase (AST) and Alanine
aminotransferase (ALT) are ≤2.5 × ULN (the upper limit of the normal range); if
liver metastasis is present, it should be ≤5 × ULN; Total bilirubin (TBIL) is ≤1.5 ×
ULN; Blood urea/urea nitrogen (UREA/BUN) and Creatinine (Cr) are ≤1.5 × ULN;
Coagulation function: International normalized ratio (INR) and Activated partial
thromboplastin time (APTT) are ≤1.5 × ULN; Urine protein is less than 2+ (if
baseline urine protein is ≥2+, a 24-hour urine protein quantification should be
performed, and it is acceptable for inclusion if ≤1g);
- 8.Women of reproductive age should agree to use contraceptive measures (such as
intrauterine devices, hormonal contraceptives, or condoms) during the study period
and for 6 months after the study ends; they must have a negative serum or urine
pregnancy test within 7 days prior to study enrollment and must not be
breastfeeding; men should agree to use contraceptive measures during the study
period and for 6 months after the study ends;
- 9.The subject can understand the nature of this study, and the subject and/or legal
representative voluntarily agrees to participate in this trial and signs the
informed consent.
Exclusion Criteria:
- 1.Patients who have previously received treatment with any HER2-targeted tyrosine
kinase inhibitors (such as lapatinib, pyrotinib, neratinib, etc.);
- 2.Those who do not meet the following requirements for the washout period from
previous anti-tumor treatments before the first administration of the study drug:
the washout time from the end of the last dose of previous anti-tumor treatment to
the first administration of the study drug (calculated from the end of the last
dose) is as follows: chemotherapy ≥3 weeks (oral fluorouracil ≥2 weeks; mitomycin C,
nitrosoureas ≥6 weeks), small molecule targeted therapy ≥2 weeks, large molecule
drugs (including immunotherapy) ≥4 weeks, radiotherapy ≥4 weeks (local palliative
radiotherapy ≥2 weeks), Chinese medicine with anti-tumor indications ≥2 weeks, other
anti-tumor treatments ≥4 weeks, investigational drugs or treatments that are not yet
marketed ≥4 weeks;
- 3.Received major organ surgery (excluding biopsy) or had significant trauma within 4
weeks before the first administration of the study drug;
- 4.Spinal cord compression or brain metastasis, unless asymptomatic, stable, and has
not required steroid treatment for at least 4 weeks before the start of the study
treatment (before dosing);
- 5.A history of other malignant tumors within the past 5 years, excluding cured
cancers such as cervical carcinoma in situ, basal cell carcinoma of the skin, or
squamous cell carcinoma of the skin;
- 6.Adverse reactions from previous anti-tumor treatments have not recovered to a
grade of ≤1 according to CTCAE 5.0 (except for toxicities judged by the investigator
to have no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, thyroid
hypothyroidism stable with hormone replacement therapy);
- 7.The presence of uncontrollable third-space fluid accumulation (such as a large
amount of pleural effusion, ascites, or pericardial effusion) that cannot be managed
by drainage or other methods;
- 8.Patients with gastrointestinal diseases that may affect drug absorption (such as
Crohn's disease, intestinal obstruction, active peptic ulcer disease, etc.);
- 9.Patients currently suffering from interstitial lung disease;
- 10.Patients with any cardiac disease, including: (1) unstable angina; (2) clinically
significant arrhythmias requiring medication; (3) myocardial infarction; (4) heart
failure of grade 3 or higher; (5) echocardiography: left ventricular ejection
fraction (LVEF) ≤50%; (6) 12-lead electrocardiogram: QTcF: females >470
milliseconds, males >450 milliseconds; (7) any other cardiac disease judged by the
investigator to be unsuitable for participating in this trial;
- 11.History of immunodeficiency, including HIV antibody test positive;
- 12.Active hepatitis B or C (HBV DNA, HCV RNA test results at screening are not
within the normal range of the central laboratory);
- 13.According to the investigator's judgment, there are other serious accompanying
diseases that endanger patient safety or affect the patient's ability to complete
the study (such as uncontrolled hypertension (systolic blood pressure ≥160 mmHg
and/or diastolic blood pressure ≥100 mmHg after taking antihypertensive drugs),
diabetes (glycated hemoglobin >9.0%), autoimmune diseases, etc.);
- 14.The investigator deems the subject unsuitable for other reasons to participate in
this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
August 10, 2024
Completion date:
April 15, 2026
Lead sponsor:
Agency:
Convalife (Shanghai) Co., Ltd.
Agency class:
Industry
Source:
Convalife (Shanghai) Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06519110
