Clinical trial NCT06144944: Neoadjuvant Pyrotinib in HR-positive and HER2-low High-risk Early Breast Cancer
Official title: Neoadjuvant Pyrotinib Combined With Chemotherapy Versus Chemotherapy in HR-positive/HER2-low (IHC 2+/FISH-negative) High-risk Early Breast Cancer: an Open-lable, Multi-center, Randomized Phase III Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer Invasive
Hormone-receptor-positive Breast Cancer
HER2 Low Breast Carcinoma
Early-stage Breast Cancer
Keywords: pyrotintb
HER2-low EBC
neoadjuvant
HR-positive
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2023-11-22
Enrollment: 160
Sex: ALL
Minimum age (years): 17
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, open-lable, prospective, randomized phase III clinical trial to further validate the efficacy and safety of neoadjuvant pyrotinib combined with chemotherapy in HR-positive/HER2-low (IHC 2+/FISH-negative) high-risk early breast cancer


Eligibility criteria: Inclusion Criteria:

* Must participate voluntarily, sign the informed consent form, and have good compliance
* Aged ≥ 18 and ≤ 70 years old with ECOG PS score of 0-1
* Histopathological newly diagnosed, unilateral, primary invasive breast cancer
* Histopathological hormone receptor-positve ( estrogen receptor and/or progesterone receptor ≥ 10% stained cells) and HER2-low (immunochemistry 2+ with fluorescent in situ hybridization negative)
* TNM stage-IIb/III, or TNM stage-IIa with high risk (N+, G3, or MammaPrint High-risk)
* At least one evaluable target breast lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* Left ventricular ejection fraction ≥ 55%, Fridericia-corrected QT interval \< 450 ms in males and \< 470 ms in females
* White blood cell count: ≥ 3.0 × 10\^9/L, absolute neutrophil count: ≥ 1.5 × 10\^9/L, platelet count: ≥ 100 × 10\^9/L, hemoglobin: ≥ 90 g/L
* Aspartate aminotransferase and alanine aminotransferase: ≤ 2.5 × ULN, alkaline phosphatase: ≤ 2.5 × ULN, blood total bilirubin: ≤ 1.5 × ULN, serum creatinine: ≤ 1.5 × ULN
* Non-menopausal or non-surgically sterilized female patients identified as non-pregnant and non-lactating and consented to contraception both during the trial and within 6 months after the last administration of the test drug

Exclusion Criteria:

* Metastatic BC, bilateral BC, occult BC, inflammatory BC, or with other malignant tumors
* Known history of hypersensitivity to the study drugs
* Patients who need receive other anti-tumor treatments (except for OFS) during neoadjuvant therapy as judged by the investigators
* With severe cardiac disease or discomfort that is not expected to tolerate treatment, including but not limited to: a) arrhythmia that requires medication or is clinically significant, or high-grade atrioventricular block, b) unstable angina, myocardial infarction, heart failure or clinically significant heart valve disease, c) poorly controlled hypertension or any heart disease unsuitable for participation in this trial as determined by the investigators
* Patients who participated in a clinical trial of another drug within 4 weeks prior to randomization or underwent BC-free surgery within 4 weeks or had not fully recovered after BC-free surgery
* Other malignancy in the past 5 years, other than cured cervical carcinoma in situ, basal or squamous cell carcinoma of skin
* Patients who had basic gastrointestinal diseases (especially long-term history of diarrhea or/and constipation), inability to swallow, intestinal obstruction or other factors will affect drugs administration and absorption
* Presence of accompanying diseases that may pose serious risks to the safety of the patient or may affect the patient's ability to complete the study (including but not limited to severe diabetes mellitus, active infection, thyroid disorders, etc.) as judged by the investigator
* With a history of immunodeficiency, including acquired or congenital immunodeficiencies, or a history of organ transplantation
* Past history of confirmed neurological or mental disorders, including epilepsy or dementia
* Other conditions of the subject determined by the investigator to be unsuitable for the study

Primary outcomes:
measure: Residual Cancer Burden 0/1 rate as assessed by independent central review
timeFrame: Within 4 weeks after surgery
Secondary outcomes:
measure: Residual Cancer Burden 0/1 rate as assessed by local pathology review
timeFrame: Within 4 weeks after surgery
measure: Pathological complete response rate
timeFrame: Within 4 weeks after surgery
measure: Objective response rate
timeFrame: Within 2 weeks of breast MR examination
measure: Breast conservation surgery rate
timeFrame: Within 4 weeks after surgery
measure: Health-related Quality of Life 1
timeFrame: Within 7 days before the first treatment and the end of each cycle (each cycle is 21 days)
measure: Health-related Quality of Life 2
timeFrame: Within 7 days before the first treatment and the end of each cycle (each cycle is 21 days)
measure: 5-year event-free survival
timeFrame: During the 5 years after random assignment
measure: 5-year overall survival
timeFrame: During the 5 years after random assignment
measure: Safety (AEs+SAEs)
timeFrame: from signing the informed consent form until 2 years after completion of neoadjuvant treatment
measure: Biomarkers (Immune cell subpopulations quantities)
timeFrame: Within 4 weeks after surgery
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
state: Guangdong
Study officials:
affiliation: Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
name: Chang Gong, Prof
role: PRINCIPAL_INVESTIGATOR
References: