First-line Treatment, HER2-positive Metastatic Breast Cancer
Conditions
Brief summary
The goal of this multicentre, randomized, double-blind controlled, phase III clinical trial is to compare the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab (THP) for newly diagnosed recurrent/metastatic Human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer, and to explore the impact of biomarkers on clinical efficacy and safety. The main questions it aims to answer are: * Analyse the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of THP. * Explore the impact of biomarkers on clinical efficacy and safety of the combination of disitamab vedotin in combination with pyrotinib treatment. Participants in the experimental group will receive disitamab vedotin in combination with pyrotinib for 6-8 cycles (each cycle lasting 28 days), followed by maintenance treatment with trastuzumab in combination with pyrotinib. Participants in the control group will receive paclitaxel in combination with trastuzumab and pertuzumab for 6-8 cycles (each cycle lasting 21 days), followed by maintenance treatment with trastuzumab and pertuzumab. Researchers will compare disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab to see if disitamab vedotin in combination with pyrotinib could be a new option for first-line treatment of HER2-positive metastatic breast cancer.
Interventions
DRUGdisitamab vedotin
disitamab vedotin 2mg/kg iv q2w
DRUGPyrotinib
pyrotinib 400mg po q28d
DRUGtrastuzumab
trastuzumab 8mg/kg for the first cycle, 6mg/kg for subsequent treatments iv q21d
DRUGPertuzumab
pertuzumab 840mg for the first cycle, 420mg for subsequent treatments iv q21d
DRUGtaxane drug
Docetaxel/paclitaxel/albumin paclitaxel/liposomal paclitaxel, dosage and administration are determined according to the latest version of the NCCN and CSCO breast cancer guideline recommendations
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Adult female patients (age 18-75 years) with metastatic breast cancer confirmed by pathology or imaging; 2. Pathologically confirmed HER2 positive (definition: Immunohistochemistry(IHC) 3+, or IHC 2+ and Fluorescent In Situ Hybridization(FISH) amplification); 3. No previous chemotherapy regimen for metastatic breast cancer; 4. At least one measurable lesion exists (Response Evaluation Criteria in Solid Tumors(RECIST) 1.1); 5. Eastern Cooperative Oncology Group(ECOG) performance status score ≤ 2 and expected survival of not less than 3 months; 6. Prior treatment-related toxicity at enrollment must have resolved to National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE) (version 5.0) ≤ 1 degree (except for alopecia or other toxicity that, in the judgment of the investigator, is not considered a risk to the safety of the patient); 7. Patients with adequate organ function before enrollment: 1. White Blood Cell (WBC) ≥ 3.0 x 10\^9/L; 2. Neutrophil granulocyte (ANC) ≥1.5 x 10\^9/L; 3. Platelet (PLT) ≥70×10\^9/L; 8. Liver, kidney, and cardiac function tests are essentially normal (based on the normal values in the laboratory of each study center): 1. Total bilirubin (TBIL) ≤ 3 x Upper Limit of Normal (ULN); 2. Alanine aminotransferase (ALT/AST) ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastases); 3. serum creatinine ≤ 1.5 x ULN or creatinine clearance (Ccr) ≥ 60 ml/min; 9. . Normal cardiac function; 1. Left ventricular ejection fraction (LVEF) ≥ 55%; 2. QT-interval corrected with Fridericia (QTcF) ≤ 470ms; 10. Hormone receptor status is clear; 11. Female patients of childbearing potential who have a negative pregnancy test and agree to use an effective non-hormonal method of contraception during treatment and for at least 6 months after the last dose of the test drug; 12. Able to understand the study process, voluntarily participate in this study, and sign an informed consent form.
Exclusion criteria
1. Pathology suggestive of HER2 negativity (IHC 2+ and FISH-, or IHC 1+); 2. Patients with known hypersensitivity to the active ingredient or other components of the study drug; 3. Patients during pregnancy or lactation, patients with childbearing potential tested positive in a baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial; 4. Patients not eligible for this study judged by the investigator, a pre-existing disease or condition that may interfere with participation in the study or any serious medical disorder that may interfere with the safety of the subject (e.g., uncontrolled heart disease, high blood pressure, active or uncontrolled infections, active hepatitis B virus infection).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Estimated 30 months | From enrollment to progression or death (for any reason) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | Estimated 30 months | Ratio of complete response (CR) , partial response (PR) and stable disease (SD) in all subjects |
| Objective Response Rate (ORR) | Estimated 30 months | Ratio of CR and PR in all subjects |
| Clinical Benefit rate (CBR) | Estimated 30 months | Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects |
| Overall Survival (OS) | Estimated 8 years | From enrollment to death (for any reason) |
| Quality of Life (QoL) by Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) | Estimated 30 months | QoL was assessed using FACT-B. FACT-B is a 37-item questionnaire with 5 subscales assessing physical, social, emotional, and functional well-being, with scores ranging from 0 to 4 for each question. Higher scores generally indicating a better quality of life. |
| Exploration of biomarkers | Estimated 30 months | Next Generation Gene Sequencing (NGS) detection of tissue and blood specimens, including ERBB1/ERBB2/ERBB3/ERBB4/AKT/TP53/PIK3CA and so on. Objective to explore the correlation between biomarkers and the objective response rate (ORR), as well as progression-free survival (PFS). |
| Adverse Events (Based on CTCAE 5.0 standards) | From informed consent through 28 days following treatment completion | Safety |
Countries
China
Outcome results
None listed