A Platform Study Based on Specific Tracer for Evaluating the Therapeutic Efficacy of Systemic Treatment for Breast Cancer Using PET/MRI

A Platform Study Based on Specific Tracer for Evaluating the Therapeutic Efficacy of Systemic Treatment for Breast Cancer Using PET/MRI (A Prospective, Open-label, Phase II Platform Trial)

This study is a prospective, open-label, phase II clinical trial, aiming to explore the predictive effect of different specific tracers on the effectiveness of various systemic treatments for breast cancer. The unique feature of this study is that it is a platform study. The research cohort can be updated accordingly as specific tracers for PET/MRI and systemic treatment regimens for breast cancer are updated. The study will be divided into two treatment cohorts: neoadjuvant therapy and salvage therapy. The research cohort will be further subdivided based on specific treatment regimens and specific tracers for PET/MRI. The subjects will undergo one 18F-FDG PET/MRI and specific tracer PET/MRI examination at baseline (before treatment) and after 2 treatment courses. This study is an exploratory phase II clinical trial, and its main purpose is to screen valuable cohorts for subsequent larger-sample randomized controlled III-phase clinical studies.

Inclusion Criteria:

1. Female patients aged 18 to 70 years.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

3. Histologically confirmed invasive breast cancer.

4. Known ER, PR and HER2 status.

5. At least one measurable lesion according to RECIST 1.1.

6. Adequate organ function, meeting all of the following:

   • Hemoglobin (Hb)≥90 g/L;
   • Absolute neutrophil count (ANC)≥1.5×10^9/L;
   • Platelet count (PLT)≥100×10^9/L;
   • Total bilirubin (TBIL)≤1.5×the upper limit of normal (ULN);
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×ULN;
   • Alkaline phosphatase (ALP)≤2.5×ULN;
   • Serum creatinine (Cr)≤1.5×ULN;
   • Prothrombin time (PT) and activated partial thromboplastin time (APTT)≤1.5×ULN, and international normalized ratio (INR)≤1.5×ULN (in patients not receiving anticoagulation).

7. Left ventricular ejection fraction (LVEF)≥55% at baseline as measured by echocardiography or multi-gated acquisition (MUGA) scan.

8. Women of childbearing potential must have a negative serum pregnancy test. Such patients must use a medically acceptable method of contraception during study treatment and for at least 6 months after the last dose of the study drug(s).

9. The subject voluntarily agrees to participate, signs the informed consent form, has good compliance, and is willing to adhere to follow-up.

Exclusion Criteria:

1. Any other malignancy within the past 5 years, except cured cervical carcinoma in situ and non-melanoma skin cancer.
2. Diabetics or those allergic to radionuclides who are not suitable for 18F-FDG PET/MR examination.
3. Serious cardiovascular or cerebrovascular disease within 6 months prior to randomization, including but not limited to congestive heart failure, unstable angina, severe arrhythmias uncontrolled by medication, severe conduction abnormalities or clinically significant valvular disease, uncontrolled severe hypertension, myocardial infarction, or cerebrovascular accident.
4. Any serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
5. Major surgery within 4 weeks prior to randomization without full recovery, or an anticipated need for major surgery during study treatment.
6. Known active liver disease, including but not limited to active hepatitis B (defined as HBsAg positive with HBV-DNA≥1000 IU/mL), hepatitis C (defined as HCV-Ab positive with HCV-RNA above the assay's lower limit of quantification), or autoimmune liver disease.
7. Severe and uncontrolled infection or known HIV infection.
8. Active systemic bacterial infection (requiring intravenous antibiotics at time of initiating study treatment) or fungal infection.
9. Pregnant or breastfeeding.
10. Known allergy to the study drug or any of its excipients, or a history of severe hypersensitivity reactions to other monoclonal antibodies.
11. Known abuse of psychotropic substances, alcoholism, or drug abuse.
12. Known, definite neurological or psychiatric disorders associated with poor compliance, including but not limited to epilepsy or dementia.
13. Any other serious physical or mental illness or laboratory abnormality that may increase the risk of study participation or interfere with study treatment and outcomes, or any other condition that, in the investigator's judgment, makes the patient unsuitable for this study.
14. Receiving radiotherapy (except for palliative reasons), chemotherapy and immunotherapy within 3 weeks before treatment, excluding bisphosphonates (can be used for bone metastasis).