Clinical trial NCT04659499: Nab-paclitaxel in Combination With Pyrotinib in Postoperative Adjuvant Therapy for HER2-positive Breast Cancer
Official title: A Multicenter, Open-label, Single-arm, Phase II Clinical Trial of Nab-paclitaxel in Combination With Pyrotinib in Adjuvant Therapy for Lymph Node-negative and Small Tumor HER2-positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Early Breast Cancer
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2020-12-09
Enrollment: 261
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, single-arm, prospective, phase II study. conducted to evaluate the efficacy, safety and tolerability of nab-paclitaxel plus pyrotinib in patients with lymph node-negative and tumor size ≤3 cm, HER2 positive breast cancer.


Eligibility criteria: Inclusion Criteria:

* Enrollment subjects must have a pathological diagnosis of HER2-positive primary invasive breast cancer with an immunohistochemistry (IHC) score of 3 +, or 2 + and HER2 gene amplification by in situ hybridization (ISH) (ratio of HER2/CEP17 ≥ 2.0).
* The invasive tumor had to measure no more than 3cm and with histologically confirmed lymph node-negative or one lymph node micrometastasis (T ≤ 3 cm, N0/N1mi, M0).
* Tumor should has known ER/PR hormone receptor status.
* All patients must be women above18 years old with Eastern Cooperative Oncology Group score 0 to 1.
* Adequate hematopoietic function and organ function as defined as follows: neutrophil count ≥ 1.5 x 109/L; Platelet count ≥ 90 × 109/L; Hemoglobin ≥ 90 g/L; total bilirubin ≤ 1.5 × ULN; alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3 × ULN; serum creatinine Cr ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula).
* left ventricular ejection fraction (LVEF) ≥ 50% and Electrocardiogram Fridericia-corrected QT interval (QTcF) ≤ 480 ms.
* Provide written informed consent.

Exclusion Criteria:

* Clinical or radiologic evidence of local or regional recurrence of disease or metastatic disease prior to or at the time of study entry.
* Previous treatment with chemotherapeutic drugs, or tyrosine kinase inhibitors targeting HER2 (lapatinib, neratinib or pyrotinib, etc.).
* Other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma.
* Inability to swallow, chronic diarrhea, or intestinal obstruction.
* Known to be allergic to the drug components.
* Have a history of immunodeficiency, including HIV positive, HCV positive, active viral hepatitis B or other immunodeficiency diseases.
* Have a history of organ transplantation.
* Pregnant, lactating female patients, or female patients who are unwilling to take effective contraceptive.
* Any heart disease, including: (1) arrhythmia; (2) myocardial infarction; (3) heart failure.
* Any other concomitant diseases assessed by investigator as unsuitable for study.
* Previous history of definite neurological or psychiatric disorders.
* Concomitant use of CYP3A4 inhibitors or inducers or drugs that prolong the QT interval.

Primary outcomes:
measure: 3-year-DFS
timeFrame: From the start of treatment to 3 years
Secondary outcomes:
measure: AEs+SAEs
timeFrame: from the first drug administration to within 28 days for the last pyrotinib dose
Other outcomes:
Locations:
Study officials:
References:
citation: Wang C, Zhou Y, Lin Y, Mao F, Guan J, Zhang X, Shen S, Wang X, Zhang Y, Pan B, Zhong Y, Peng L, Cao X, Yao R, Zhou X, Xu C, Xu Y, Sun Q. Rationale and design of a phase II trial of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for N0/N1mi, HER2 + early breast cancer (PHAEDRA). BMC Cancer. 2022 Mar 14;22(1):269. doi: 10.1186/s12885-022-09346-1.