A Clinical Study on Hormone Receptor Positive HER2 Positive Breast Cancer of RCB1-2 After Neoadjuvant Treatment with Trastuzumab Combined with Parezumab

Launched by SUN YAT-SEN MEMORIAL HOSPITAL OF SUN YAT-SEN UNIVERSITY · Feb 26, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for women with early-stage breast cancer that is both hormone receptor positive and HER2 positive. Specifically, it is comparing the effectiveness and safety of two different drug combinations: one that includes trastuzumab and neratinib, and another that uses trastuzumab and patuzumab. The goal is to see which combination helps prevent the cancer from coming back after initial treatment has been completed.

To be eligible for this study, participants must be women between the ages of 18 and 70 who have been diagnosed with this specific type of breast cancer and have undergone initial treatment but still have some cancer remaining. Participants will be randomly assigned to one of the two treatment groups and will receive regular check-ups to monitor their progress. It’s important to note that this study is currently recruiting participants, and women who decide to join will need to agree to certain health and safety guidelines. This trial aims to provide valuable insights into the best ways to treat this type of breast cancer after initial therapy.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • 1. Female patients ≥ 18 years old and ≤ 70 years old;
• • 2. ECOG score 0-1;
• • 3. The clinical staging at the time of initial diagnosis (according to the 8th edition of the American Joint Commission on Cancer \[AJCC\] Cancer Staging Manual): cT4/any N/M0, any cT/N2 - 3/M0 or cT1-3/N0-1/M0 (cT1mi/T1a/T1b/N0 patients are not eligible) at the time of initial diagnosis meets the new adjuvant treatment standard (NCCN2022 guidance of the National Comprehensive Cancer Network of the United States). The primary invasive lesions and lymph nodes of the breast must meet the following conditions: histologically confirmed invasive breast cancer; After receiving the new adjuvant treatment and completing the surgery, the pathology showed that there was residual invasive cancer in the breast or axillary lymph nodes and the RCB rating was 1-2; HER2 pathological test result is positive, which is defined as the result of immunohistochemistry (IHC) test is 3+or the result of in situ hybridization (ISH) is HER2 gene amplification (HER2/CEP17 ≥ 2.0 or average HER2 copy number/cell ≥ 6); There was no recurrence or metastatic disease before adjuvant treatment after operation.
• • 4. Trastuzumab+Parstuzumab were applied in the new auxiliary stage and the treatment time was ≥ 12 weeks or 4 dosing cycles. No residual lesions were found at the resection margin of breast surgery specimen. Axilla can accept sentinel lymph node biopsy or axillary lymph node dissection (patients receiving axillary lymph node biopsy should meet the NCCN guidelines for sentinel lymph node biopsy after new adjuvant treatment). The operation and pathology showed that HER2 positive breast cancer patients did not reach complete pathological remission (non pCR) and RCB grade was 1-2. The time from initial operation to randomization was less than 12 weeks;
• • 5. Hormone receptor positive (definition: immunohistochemistry estrogen receptor ≥ 1%, and/or progesterone receptor ≥ 1%), HER2 positive (definition: standard immunohistochemistry 3+or ISH positive);
• 6. The functional level of the main organs must meet the following requirements (no blood transfusion, no use of leukopenia and platelet raising drugs within 2 weeks before screening):
• • Neutrophil (ANC) ≥ 1.5 × 109/L；
• • Platelet count (PLT) ≥ 90 × 109/L；
• • Hemoglobin (Hb) ≥ 90 g/L;
• • Total bilirubin (TBIL) ≤ 1.5 × Upper limit of normal value (ULN);
• • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN；
• • 7. After the completion of neoadjuvant therapy, echocardiography (ECHO) showed that the left ventricular ejection fraction (LVEF) in the screening period was ≥ 50% and the absolute decrease of LVEF was not more than 15% compared with that before chemotherapy. Or, if LVEF evaluation is not performed before chemotherapy, LVEF must be ≥ 55% in the screening period after completion of neoadjuvant therapy
• • 8. Expected life ≥ 6 months
• • 9. For female patients who have not undergone menopause or surgical sterilization: during the study treatment and within 8 weeks after the last administration of the drug during the study treatment, they agree to abstain or use effective non hormone contraceptive methods;
• • 10. Volunteer to participate in the trial, sign the informed consent form, have good compliance and are willing to cooperate with follow-up.
• Exclusion Criteria:
• • 1. Recurrent disease of local or regional breast has occurred in the past;
• • 2. The clinical staging of the tumor is stage IV (metastatic) breast cancer;
• • 3. Bilateral breast cancer;
• • 4. Any history of malignant tumors other than breast cancer in the past 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma or squamous cell carcinoma;
• • 5. He has previously received treatment including pyrrolidine, lapatinib, neratinib or other tyrosine kinase inhibitors, entetrazumab (T-DM1), and other anti-tumor biological therapy or tumor immunotherapy;
• • 6. At the same time, he received anti-tumor therapy in other clinical trials, including endocrine therapy, bisphosphonate therapy or immunotherapy;
• • 7. Serious heart disease or discomfort, including but not limited to the following diseases: history of diagnosis of heart failure or systolic dysfunction (LVEF\<50%); High risk uncontrolled arrhythmia, such as atrial tachycardia, significant ventricular arrhythmia (such as ventricular tachycardia) or higher grade atrioventricular block; Angina pectoris requiring anti angina drugs; Valvular heart disease with clinical significance; ECG showed transmural myocardial infarction; The blood pressure of hypertensive patients was not well controlled by drugs (systolic blood pressure\>180 mmHg and/or diastolic blood pressure\>100 mmHg);
• • 8. Inability to swallow, intestinal obstruction or other factors affecting drug administration and absorption;
• • 9. Have a history of previously diagnosed neurological or mental disorders, including patients with involuntary behavior or mental illness;
• • 10. Previous history of gastrointestinal diseases with diarrhea as the main symptom;
• • 11. People who are known to have a history of allergy to the drug components of this protocol; Have a history of immunodeficiency, including HIV test positive, or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation;
• • 12. Female patients in pregnancy and lactation, female patients with fertility and positive baseline pregnancy test;
• • 13. Suffering from serious concomitant diseases or other concomitant diseases that will interfere with the planned treatment, including infectious diseases with active infection (including but not limited to active hepatitis B, active hepatitis C, active tuberculosis, active syphilis, etc.), or any other circumstances in which the researcher believes that the patient is not suitable to participate in the test.