Breast Cancer
Conditions
Keywords
breast cancer
Brief summary
This study evaluates HER2-PET/CT-guided dynamic optimization of neoadjuvant therapy in patients with early-stage HER2-positive breast cancer. Based on metabolic response after two cycles, patients receive either intenstified treatment (Arm A) or de-escalation treatment (Arm B), alongside with a concurrent standard-treatment control group (Arm C). The study aims to establish a response-adaptive, imaging-guided treatment paradigm to optimize neoadjuvant therapy in HER2-positive breast cancer.
Detailed description
This is a prospective, two-arm, interventional study. Eligible patients with early-stage HER2-positive breast cancer are enrolled into Arm A (TCbHP: trastuzumab, pertuzumab, docetaxel/nab-paclitaxel, and carboplatin) or Arm B (trastuzumab, pertuzumab, CDK4/6 inhibitor, and aromatase inhibitor), based on molecular subtype and patient preference. Patients in the control group (ArmC) will receive standard TCbHP therapy without intervention. All patients will undergo HER2-PET/CT imaging at baseline and after two cycles of treatment. Metabolic response, defined as a ≥40% reduction in SUVmax of target lesions, guides subsequent therapy: responders continue the initial regimen, while non-responders switch to an alternative strategy (ADC in Arm A or TCbHP in Arm B). The primary endpoint is the total pathological complete response (tpCR) rate in Arm A and ArmB.
Interventions
8 mg/kg first dose, followed 6 mg/kg given into the vein (IV; intravenously) every 21 days
DRUGPertuzumab
840 mg first dose, followed 420 mg given by IV every 21 days
600 mg Pertuzumab, 600 mg Trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days
DRUGDocetaxel or Nab-paclitaxel
Docetaxe 75mg/m²/ Nab-paclitaxel：260mg/m²
DRUGcarboplatin
AUC6
DRUGCDK4/6 inhibitor
Ribociclib 600mg once daily every 21days/ Dalpiciclib 150mg once daily every 21days/ Palbociclib 125mg once daily every 21days
Letrozole 2.5mg once daily/ Anastrozole 1mg once daily/ Exemestane25mg once daily
DRUGADC
T-Dxd: 5.4mg/kg given into the vein (IV; intravenously) every 21 days SHR-A1811: 4.8mg/kg given into the vein (IV; intravenously) every 21 days
Sponsors
Peking University Cancer Hospital & Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Voluntary participation with written informed consent obtained prior to any study-related procedures * Age ≥ 18 years, male or female. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 * Histologically confirmed HER2-positive (IHC 3+, or IHC 2+ with ISH amplification) stage I-III (cT1-3/cN0-2) breast cancer * Tumor diameter ≥ 1.5 cm assessed by imaging, with at least one PET-evaluable lesion present * Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status. For Arm B, ER expression ≥ 10% and must be strongly positive. * Adequate bone marrow, liver, and renal function: WBC \> 3.0 × 10⁹/L, ANC ≥ 1.5 × 10⁹/L, PLT ≥ 100 × 10⁹/L, Hb ≥ 10.0 g/dL; total bilirubin ≤ ULN (excluding Gilbert's syndrome), ALP ≤ 2.5 × ULN, AST/ALT ≤ 1.5 × ULN; creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min. * Patients who participate in the trial have good compliance and are willing to comply with the follow-up visit.
Exclusion criteria
* Prior treatment with any chemotherapy, anti-HER2 therapy, radiotherapy, or endocrine therapy, etc * Locally advanced (cT4/cN3) or bilateral breast cancer * Patients with known allergies to any active ingredients or excipients of investigational medicinal product * Other malignancy diagnosed within 5 years prior to enrollment, excluding cervical carcinoma in situ and cured melanoma skin cancer * Left ventricular ejection fraction (LVEF) \< 55% * Uncontrolled hypertension (systolic \> 150 mm Hg and/or diastolic \> 100 mm Hg) * Severely cardiovascular disease * Current known infection with HIV, hepatitis B virus, or hepatitis C virus * Patients with pulmonary disease requiring continuous oxygen therapy, previous history of bleeding diathesis or patient is currently receiving anti-coagulant therapy, or immunosuppressive agent * Major surgical procedure or significant traumatic injury * Patient has other concurrent severe and/or uncontrolled medical conditions. * Concurrent participation in other interventional clinical trial * History of receiving any investigational treatment within 28 days prior to randomization * Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol * Inability to lie flat or presence of psychiatric disorders such as claustrophobia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| rate of pathologic complete response (pCR) | Up to 6 months after treatment start | Proportion of participants who have no evidence by H\&E staining of residual invasive disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SUVmax change on HER2-PET | Up to 6 months after treatment start | The change in SUVmax value of HER2-PET after 2 cycles of treatment compared to the baseline level |
Contacts
CONTACTXu Liang
Outcome results
None listed