Neoadjuvant Pyrotinib Versus Placebo Combined With Chemotherapy in HR-positive and HER2-low Early Breast Cancer

Sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06144944

Collaborator

Jiangsu HengRui Medicine Co., Ltd. (Industry)

160

Enrollment

Location

Arms

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multi-center, double blind, prospective, placebo controlled, 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) early breast cancer

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Invasive Hormone-receptor-positive Breast Cancer HER2 Low Breast Carcinoma Early-stage Breast Cancer	Drug: Pyrotinib, epirubicin or doxorubicin, cyclophosphamide, paclitaxel Drug: Placebo, epirubicin or doxorubicin, cyclophosphamide, paclitaxel	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Neoadjuvant Pyrotinib Versus Placebo Combined With Chemotherapy in HR-positive/HER2-low (IHC 2+/FISH-negative) Early Breast Cancer: a Double Blind, Multi-center, Randomized Phase III Trial

Anticipated Study Start Date :

Jan 1, 2024

Anticipated Primary Completion Date :

Jun 30, 2026

Anticipated Study Completion Date :

Dec 31, 2031

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neoadjuvant pyrotinib combined with chemotherapy	Drug: Pyrotinib, epirubicin or doxorubicin, cyclophosphamide, paclitaxel Pyrotinib 320 mg orally once daily, and epirubicin 90 mg/m² or doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² intravenously on day 1 for four 3-week cycles followed by paclitaxel 175 mg/m² intravenously on day 1 or four 3-week cycles.
Placebo Comparator: Neoadjuvant chemotherapy	Drug: Placebo, epirubicin or doxorubicin, cyclophosphamide, paclitaxel Placebo orally once daily, and epirubicin 90 mg/m² or doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² intravenously on day 1 for four 3-week cycles followed by paclitaxel 175 mg/m² intravenously on day 1 or four 3-week cycles.

Arm

Intervention/Treatment

Experimental: Neoadjuvant pyrotinib combined with chemotherapy

Drug: Pyrotinib, epirubicin or doxorubicin, cyclophosphamide, paclitaxel

Pyrotinib 320 mg orally once daily, and epirubicin 90 mg/m² or doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² intravenously on day 1 for four 3-week cycles followed by paclitaxel 175 mg/m² intravenously on day 1 or four 3-week cycles.

Placebo Comparator: Neoadjuvant chemotherapy

Drug: Placebo, epirubicin or doxorubicin, cyclophosphamide, paclitaxel

Placebo orally once daily, and epirubicin 90 mg/m² or doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² intravenously on day 1 for four 3-week cycles followed by paclitaxel 175 mg/m² intravenously on day 1 or four 3-week cycles.

Outcome Measures

Primary Outcome Measures

Residual Cancer Burden 0/1 rate as assessed by independent central review [Within 4 weeks after surgery]
The proportion of patients with RCB 0/I after neoadjuvant therapy according to the online Residual Cancer Burden Calculator provided by the MD Anderson Cancer Center as assessed by independent central review

Secondary Outcome Measures

Residual Cancer Burden 0/1 rate as assessed by local pathology review [Within 4 weeks after surgery]
The proportion of patients with RCB 0/I after neoadjuvant therapy according to the online Residual Cancer Burden Calculator provided by the MD Anderson Cancer Center as assessed by local pathology review
Pathological complete response rate [Within 4 weeks after surgery]
The proportion of patients with no residual invasive tumor cells in the breast and axillary nodes, regardless of ductal carcinoma in situ
Objective response rate [Within 2 weeks of breast MR examination]
The percentage of patients who achieved a complete or partial response in breast according to the RECIST, version 1.1, based on MRI, at the end of cycle 2 neoadjuvant therapy and at the end of cycle 8 neoadjuvant therapy
Breast conservation surgery rate [Within 4 weeks after surgery]
The proportion of patients who had successful breast conservation surgery after neoadjuvant therapy
Health-related Quality of Life 1 [Within 7 days before the first treatment and the end of each cycle (each cycle is 21 days)]
The score of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (version 3)
Health-related Quality of Life 2 [Within 7 days before the first treatment and the end of each cycle (each cycle is 21 days)]
The score of Breast Cancer-Specific Module (QLQ-BR23)
5-year event-free survival [During the 5 years after random assignment]
the time from random assignment until any relapse, unequivocal tumor progression, or any-cause death
5-year overall survival [During the 5 years after random assignment]
the time from random assignment until any-cause death
Safety (AEs+SAEs) [from signing the informed consent form until 2 years after completion of neoadjuvant treatment]
General safety will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Ovarian toxicity will be evaluated by menstrual status and FSH and E2
Biomarkers (Immune cell subpopulations quantities) [Within 4 weeks after surgery]
The association between immune cell subpopulations quantities and RCB

Eligibility Criteria

Criteria

Ages Eligible for Study:

17 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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, G2 with Ki67 ≥ 20%)
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