Optimization of Dynamic Neoadjuvant Therapy Strategies for HER2-Positive Breast Cancer Based on HER2-PET/CT Molecular Imaging

Official title

A Prospective, Double-Arm Study on the Optimization of Dynamic Neoadjuvant Therapy Strategies for HER2-Positive Breast Cancer Based on HER2-PET/CT Molecular Imaging

Overview

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

• Drug Trastuzumab (Herceptin)
  8 mg/kg first dose, followed 6 mg/kg given into the vein (IV; intravenously) every 21 days
• Drug Pertuzumab
  840 mg first dose, followed 420 mg given by IV every 21 days
• Drug Combination product: Trastuzumab + Pertuzumab
  600 mg Pertuzumab, 600 mg Trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days
• Drug Docetaxel or Nab-paclitaxel
  Docetaxe 75mg/m²/ Nab-paclitaxel：260mg/m²
• Drug carboplatin
  AUC6
• Drug CDK4/6 inhibitor
  Ribociclib 600mg once daily every 21days/ Dalpiciclib 150mg once daily every 21days/ Palbociclib 125mg once daily every 21days
• Drug Aromatase Inhibitor (AI)
  Letrozole 2.5mg once daily/ Anastrozole 1mg once daily/ Exemestane25mg once daily
• Drug ADC
  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

Primary outcome measures

• rate of pathologic complete response (pCR) [Time frame: Up to 6 months after treatment start]

Secondary outcome measures (1)

• SUVmax change on HER2-PET [Time frame: Up to 6 months after treatment start]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07527806 · L259061

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗