Clinical trial NCT05165225: Phase II Neoadjuvant Pyrotinib Combined with Neoadjuvant Chemotherapy in HER2-low-expressing and HR Positive Early or Locally Advanced Breast Cancer: a Single-arm, Non-randomized, Single-center, Open Label Trial
Official title: Phase II Neoadjuvant Pyrotinib Combined with Neoadjuvant Chemotherapy in HER2-low-expressing and HR Positive Early or Locally Advanced Breast Cancer: a Single-arm, Non-randomized, Single-center, Open Label Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
HER2-low-expressing Breast Cancer
Hormone Receptor-positive Breast Cancer
Neoadjuvant Therapy
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2021-12-21
Enrollment: 48
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, prospective, non-randomized, single-center, open label clinical study for evaluating the efficacy and safety of neoadjuvant pyrotinib combined with epirubicin and cyclophosphamide followed by docetaxel in HR positive and HER2-low-expressing early or locally advanced breast cancer.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent for all study according to local regulatory requirements prior to beginning specific protocol procedures
2. Female patients, age ≥ 18 years
3. Histologically confirmed unilateral primary carcinoma of the breast, except for occult breast cancer, inflammatory breast cancer without assessable focus or eczema like breast cancer
4. HER2-low-positive (defined here as HER2 IHC 2+ and FISH-) and HR positive(defined here as ER and/or PR \>1% stained cells)
5. Tumour greater than 2 cm diameter or histologically (core- or fine-needle biopsy) involved lymph nodes
6. According to RECIST version 1.1, there is at least one evaluable target lesion
7. Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1
8. Required laboratory values including following parameters: WBC count:≥3.0 x 10\^9/L ; ANC: ≥ 1.5 x 10\^9/L; Platelet count: ≥ 100 x 10\^9/L; Hemoglobin: ≥ 9.0 g/dL; Total bilirubin: ≤ 1.5 x upper limit of normal (ULN); ALT and AST: ≤ 2.5 x ULN; alkaline phosphatase ≤ 2.5 × ULN; Serum creatinine: ≤ 1.5 × ULN; Left ventricular ejection fraction (LVEF) ≥ 55%
9. For female patients without menopause or surgical sterilization: consent to contraception both during the trial and within 6 months after the last administration of the test drug

Exclusion Criteria:

1. Metastatic disease (Stage IV) or bilateral breast cancer
2. Known history of hypersensitivity to pyrotinib or any of it components
3. According to the judgment of the researcher, other anti-tumor treatments (except for ovarian function inhibitors) are required during neoadjuvant therapy
4. Patients with severe heart disease or discomfort who are expected to be unable to tolerate chemotherapy, including but not limited to these: 1). Fatal arrhythmia or higher grade atrioventricular block (second degree type 2 atrioventricular block or third degree atrioventricular block) 2). Unstable angina pectoris 3). Heart valve disease with clinical significance 4). ECG showed transmural myocardial infarction pain 5). Poor control of hypertension
5. Patients underwent major breast cancer-free surgery within 4 weeks or have not fully recovered
6. Serious or uncontrolled infections that may affect study treatment or evaluation of study results, including but not limited to active hepatitis virus infection, human immunodeficiency virus (HIV) antibody positive, lung infection, etc
7. History of other malignant tumors in the past 5 years (excluding cured carcinoma in situ of cervix or skin basal cell carcinoma)
8. Those with basic gastrointestinal diseases (especially long-term history of diarrhea or/and constipation)；Inability to swallow、intestinal obstruction or other factors will affect drug administration and absorption
9. The investigator believes that the patient has any other conditions that are not suitable for participation in the study

Primary outcomes:
measure: Residual cancer burden 0/1 (RCB-0/1) rate
timeFrame: within 6 weeks after surgery
Secondary outcomes:
measure: Pathological complete response (pCR) rate
timeFrame: within 6 weeks after surgery
measure: Objective response rate (ORR)
timeFrame: within 6 weeks after surgery
measure: Breast conservation rate.
timeFrame: within 6 weeks after surgery
measure: Disease-free Survival (DFS)
timeFrame: 5 years
measure: Overall Survival (OS).
timeFrame: 5 years
measure: Biomarkers
timeFrame: 5 years
measure: Incidence of grade 3-5 diarrhea.
timeFrame: before surgery
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
state: Guangdong
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Gong - Chang, doctor
role: PRINCIPAL_INVESTIGATOR
References: