Pyrotinib in Combination With Neoadjuvant Chemotherapy in HR+/HER2-, HER4 High Expression Breast Cancer Patients: A Phase II Trial

• Status: Recruiting
• Trial end date: 2028-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase II, single-center, double-blind, placebo-controlled, randomized study of Pyrotinib in combination with Doxorubicin/Epirubicin and Cyclophosphamide followed by Docetaxel/nab-Paclitaxel as neoadjuvant therapy for women with hormone receptor positive HER2-negative stage II to III breast cancer. Patients randomized to the study arm/control arm will receive standard neoadjuvant chemotherapy in combination with pyrotinib/placebo, respectively. The primary endpoint of the study is the total pathological complete response (pCR) rate. Secondary endpoints include the pCR rate in breast only, objective response rate(ORR), event-free survival, overall survival, and toxicity. We will also explore potential prognostic and predictive biomarkers.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Collaborator: Jiangsu HengRui Medicine Co., Ltd.
• Treatments: Cyclophosphamide; Docetaxel; Doxorubicin; Epirubicin; Liposomal doxorubicin; Paclitaxel

Criteria

Inclusion Criteria:

• Presenting with histological(by core needle biopsy or by limited incisional biopsy) proven hormone receptor positive (ER≥10% and/or PR ≥1%), HER2 negative(IHC ≤2+ and/or FISH-) , stage II/ III breast cancer.

• Have clinical indication for neoadjuvant therapy.

• HER4 IHC score ≥ 4.

• Measurable disease (breast and/or lymph nodes).

• The Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1.

• Adequate bone marrow function (within 4 weeks prior to registration): WBC≥3.0x109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l.

• Adequate liver function (within 4 weeks prior to registration): bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL.

• Adequate renal function (within 4 weeks prior to registration): the calculated creatinine clearance should be ≥50 ml/min.

• Patients must have the ability to swallow oral medication.

• Without history of any kind of treatment to known malignancy (solid tumor or hematologic).

• Written informed consent.

• Accessible for treatment and follow-up.

Exclusion Criteria:

• Evidence of stage IV breast cancer.

• Contralateral invasive breast cancer or Inflammatory breast cancer.

• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization.

• Known metastatic disease from any malignancy (solid tumor or hematologic).

• Serious other diseases as infections (hepatitis B, C and HIV), recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias or on screening, any of the following cardiac parameters: bradycardia (heart rate <50 at rest) or QTcF ≥450 msec.

• Known hypersensitivity reaction to any of the components of the treatment.

• Pregnancy or lactation at the time of randomization.

• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent.