Breast Cancer Females
Conditions
Keywords
Breast cancer, Antibody drug conjugate, Timing of application, Randomized controlled trial, HER2-negative
Brief summary
This study plans to initiate a prospective, randomized controlled trial to investigate the optimal timing of antibody drug conjugate (ADC) therapy in the management of advanced Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer. Primary Objective: To compare the difference in PFS2 (Time from randomization to disease progression after second therapy) between antibody-drug conjugate (ADC) followed by chemotherapy versus chemotherapy followed by ADC in the treatment of advanced HER2-negative breast cancer. Secondary Objectives: To compare overall survival (OS), adverse events, patient-reported outcomes, and cost-effectiveness between the two treatment sequences. Additionally, to identify potential biomarkers predictive of benefit from frontline ADC therapy.
Interventions
DRUGAntibody drug conjugate
The selection of ADC agents will be based on the patient's molecular subtype. For Hormone receptor (HR)+/HER2-low patients, anti-HER2 ADCs such as trastuzumab deruxtecan may be used. For HR+/HER2-zero patients, TROP-2-targeted ADCs such as sacituzumab govitecan are preferred. For HR-/HER2-low patients, either anti-HER2 ADCs or Trophoblast cell surface antigen 2 (TROP-2) ADCs may be considered. For HR-/HER2-zero patients, TROP-2 ADCs will be used. The specific ADC regimen will be determined at the discretion of the investigators.
DRUGChemotherapy
The chemotherapy regimen will consist of standard second-line agents such as capecitabine, eribulin, vinorelbine, or gemcitabine. The specific chemotherapy regimen will be determined at the discretion of the investigators.
Sponsors
Liaoning Cancer Hospital & Institute
National Cancer Center, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Female patients aged 18-75 years; 2. Histologically confirmed advanced HER2-negative breast cancer, including IHC 2+/ISH-, IHC 1+/ISH-, and IHC 0/ISH- subtypes; 3. Completed first-line combination chemotherapy for advanced/metastatic disease (specific regimen not restricted), with disease progression (PD) evaluated per RECIST criteria (HR-positive patients must have received at least one line of endocrine therapy); 4. Electrocorticography (ECOG) performance status \< 2; 5. Estimated life expectancy ≥ 12 weeks; 6. Adequate bone marrow function, defined as: * ANC ≥ 1.5 × 10⁹/L * Platelets ≥ 90 × 10⁹/L * Hemoglobin ≥ 90 g/L 7. Adequate hepatic and renal function, defined as: * Total bilirubin ≤ 1.5 × upper limit of normal (ULN) * AST or ALT ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases) * Creatinine clearance ≥ 60 mL/min 8. Signed informed consent obtained prior to any study-related procedures or treatments, confirming the patient's willingness to participate and comply with study requirements.
Exclusion criteria
1. Prior treatment with an ADC after disease recurrence or metastasis; 2. Pregnant or breastfeeding women; 3. No evaluable recurrent or metastatic lesions as defined by RECIST 1.1 criteria; 4. Symptomatic brain parenchymal and/or leptomeningeal metastases with symptoms not adequately controlled by treatment; 5. History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix, cutaneous squamous cell carcinoma, or well-controlled localized basal cell carcinoma of the skin; 6. Psychiatric disorders or other conditions that may interfere with patient compliance; 7. Recent history of serious and uncontrolled systemic diseases, such as clinically significant cardiovascular disease, pulmonary disease, metabolic disorders, or arterial/venous thromboembolic events; 8. Concurrent use of other investigational drugs, or participation in another clinical trial within 30 days prior to enrollment; 9. Known or suspected allergy to any study drug or its excipients; 10. Any other condition that, in the opinion of the investigator, renders the patient unsuitable for participation in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival 2 (PFS2) | Up to approximately 20 months | Progression-free survival 2 (PFS2) is defined as the time from randomization to disease progression or death (whichever occurs first) following the second treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 40 months | Defined as the time from randomization to death from any cause. |
| Patient-Reported Outcomes (PROs) | Up to approximately 20 months | Defined as reports directly from patients regarding their health status, functional status, and treatment experience during the period from randomization to disease progression, without interpretation by clinicians or others. |
| Time to Progression (TTP) | Up to approximately 20 months | Defined as the time from randomization to disease progression. |
| Adverse event | Up to approximately 20 months | Defined as the occurrence of adverse events after enrollment, evaluated according to NCI CTCAE version 5.0. |
Countries
China
Contacts
CONTACTDan Lyu
PRINCIPAL_INVESTIGATORTao Sun
Liaoning Cancer Hospital & Institute
PRINCIPAL_INVESTIGATORBo Lan
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital
Outcome results
None listed