Clinical trial NCT04900311: Pyrotinib Versus Pertuzumab in Combination With Neoadjuvant Trastuzumab and Nab-Paclitaxel in HER2+ Early or Locally Advanced Breast Cancer
Official title: Pyrotinib Versus Pertuzumab in Combination With Neoadjuvant Trastuzumab and Nab-Paclitaxel in HER2+ Early or Locally Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: HER2+ Early or Locally Advanced Breast Cancer
Keywords: HER2+ breast cancer
neoadjuvant
pyrotinib
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
Collaborators: name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
First posted: 2021-05-25
Enrollment: 490
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is being conducted to evaluate the efficacy, and safety of pyrotinib versus pertuzumab in combination with trastuzumab and nab-paclitaxel for neoadjuvant treatment in HER2+ early or locally advanced breast cancer patients. To explore whether pyrotinib regimen could provide better clinical results compared with pertuzumab in the study population.

Detailed description: This study is a multi-center, randomized, open-label, controlled trial. Eligible patients will be randomized to neoadjuvant pyrotinib or pertuzumab containing regimen every 3 weeks for four cycles before surgery. Randomization was stratified by the following factors: hormone receptor status and primary tumor size. After completing four cycles of neoadjuvant treatment, all patients who are eligible for surgery will undergo surgery and have their pathologic response evaluated. Following surgery, patients will receive 90-100 mg/m2 epirubicin and 600 mg/m2 cyclophosphamide every 3 weeks for 4 cycles. Clinicians will select subsequent treatments for patients based on guidelines as well as clinical practice at each site.

Eligibility criteria: Inclusion Criteria:

* female patients, treatment-naïve, aged ≥ 18 years and ≤ 75 years;
* ECOG score 0-1 (ECOG, Eastern Cooperative Oncology Group);
* Histologically confirmed invasive breast cancer (early stage or locally advanced) :Primary tumor greater than 2 cm diameter and cT2-cT4/cN0-cN3/cM0 (clinical stage II and III);
* HER2 expression positive breast cancer confirmed by pathological examination,
* known hormone receptor status (ER and PR);
* the level of major organ function must meet the following requirements: blood routine test: neutrophil (ANC) ≥ 1.5 × 109/L; platelet count (PLT) ≥ 90 × 109/L; hemoglobin (Hb) ≥ 90g/L; blood biochemistry test: total bilirubin (TBIL) ≤ 2.5 × ULN (upper normal limit); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; blood urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN; echocardiography: LVEF ((Left Ventricular Ejection Fraction) ≥ 55%; 12 ECG: QT interval corrected by Fridericia method (QTcF) \< 470 ms in women
* Female subjects who have not yet experienced menopausal or not surgically sterile agree to practice abstinence or use effective methods of contraception for at least 7 months during and after the last dose of study drug;
* Sign the informed consent form and are willing to cooperate in the follow-up.

Exclusion Criteria:

* breast cancer of both sides, stage IV breast cancer or metastatic breast cancer;
* inflammatory breast cancer;
* History of other malignancy, or previous anti-cancer therapy or radiotherapy for any malignancy, excluding cured carcinoma in situ of the cervix or squamous or basal cell carcinoma.
* simultaneously participated in other clinical trials;
* Major surgical procedure unrelated to breast cancer within 4 weeks prior to randomization or from which the patient has not fully recovered
* blood transfusion, or received colony-stimulating factor treatments before randomization;
* known history of allergy to any of the study medications and any of the ingredients or excipients of these medications;
* history of immunodeficiency, including positive HIV test, or suffering from other acquired, congenital immunodeficiency diseases, or history of organ transplantation.
* had any heart disease, including: (1) angina pectoris; (2) arrhythmia that is clinically significant or required medication; (3) myocardial infarction; (4) heart failure; (5) any other heart disease judged by the investigator as not suitable for this trial.
* pregnant or lactating
* Other concurrent serious diseases that are serious hazards to the patient's safety or may interfere with planned treatment (including but not limited to hypertension, severe diabetes, active infection, thyroid disease, etc.) ;
* Inability to swallow, chronic diarrhea, bowel obstruction, and other factors affecting medication intake and absorption.
* Any other condition that, in the opinion of the investigator, makes the subject unsuitable for this study.

Primary outcomes:
measure: tpCR (totally pathological Complete Response) assessed by the IRC(Independent Review Committee)
timeFrame: Pathologic response will be evaluated right after surgery, which will be performed within 14 days after the completion neoadjuvant therapy (four cycles, 21 days per cycle).
Secondary outcomes:
measure: iDFS (Invasive disease-free survival)
timeFrame: from the date of surgery till two years after study-defined treatment.
measure: EFS (event free survival)
timeFrame: from the date of surgery till two years after study-defined treatment.
measure: ORR (Objective Response Rate)
timeFrame: At the end of neoadjuvant therapy (four cycles, 21 days per cycle).
measure: the rate of adopting breast-conserving surgery
timeFrame: evaluated right after surgery, which will be performed within 14 days after the completion neoadjuvant therapy (four cycles, 21 days per cycle).
Other outcomes:
measure: Incidence of serious adverse events and other adverse events of special interest
timeFrame: through study completion, an average of 2.5 years.
measure: Exploratory biomarker analyses
timeFrame: through study completion, an average of 2.5 years.
Locations:
Study officials:
References: