Clinical Trials /

Pyrotinib in Breast Cancer Patients With Poor Response to the Neoadjuvant Treatment of Trastuzumab and Pertuzumab

NCT04255056

Description:

Pathological complete remission (pCR) after neoadjuvant therapy in HER2-positive early breast cancer patients is closely related to disease-free survival (DFS) and overall survival (OS), which makes pCR an important evaluation indicator of recurrence risk. Trastuzumab combined with pertuzumab is a new standard targeted treatment regimen for HER2-positive early breast cancer. However, there are still quite a few patients who do not reach PCR. For these patients, current guidelines recommend the use of TDM-1 for intensive treatment after surgery, although a significant number of patients still have recurrence or metastasis. Besides, TDM-1 is unavailable in China. Pyrotinib has been approved for HER2-positive breast cancer patients who have previously failed after the treatment of trastuzumab. The investigators intend to conduct this phase II clinical study. Patients with poor response to the standard neoadjuvant treatment regimen of trastuzumab combined with pertuzumab are enrolled. These patients receive pyrotinib to observe that whether pCR has been improved. The investigators aim to explore the effect of pyrotinib in patients with poor response to standard dual-target neoadjuvant therapy, and further explore the improvement of neoadjuvant treatment strategy in HER2 positive early stage breast cancer patients.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pyrotinib in Breast Cancer Patients With Poor Response to the Neoadjuvant Treatment of Trastuzumab and Pertuzumab
  • Official Title: The Effect of Pyrotinib in Breast Cancer Patients With Poor Response to the Neoadjuvant Treatment of Trastuzumab Combined With Pertuzumab: A Single-center Phase II Clinical Study

Clinical Trial IDs

  • ORG STUDY ID: SYSU-CSCO-2020
  • NCT ID: NCT04255056

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Pyrotinibepirubicin, cyclophosphamidePyrotinib

Purpose

Pathological complete remission (pCR) after neoadjuvant therapy in HER2-positive early breast cancer patients is closely related to disease-free survival (DFS) and overall survival (OS), which makes pCR an important evaluation indicator of recurrence risk. Trastuzumab combined with pertuzumab is a new standard targeted treatment regimen for HER2-positive early breast cancer. However, there are still quite a few patients who do not reach PCR. For these patients, current guidelines recommend the use of TDM-1 for intensive treatment after surgery, although a significant number of patients still have recurrence or metastasis. Besides, TDM-1 is unavailable in China. Pyrotinib has been approved for HER2-positive breast cancer patients who have previously failed after the treatment of trastuzumab. The investigators intend to conduct this phase II clinical study. Patients with poor response to the standard neoadjuvant treatment regimen of trastuzumab combined with pertuzumab are enrolled. These patients receive pyrotinib to observe that whether pCR has been improved. The investigators aim to explore the effect of pyrotinib in patients with poor response to standard dual-target neoadjuvant therapy, and further explore the improvement of neoadjuvant treatment strategy in HER2 positive early stage breast cancer patients.

Detailed Description

      Breast cancer is the most common malignant tumor in Chinese women, with 20% to 30% HER2
      overexpression. Pathological complete remission (pCR) after neoadjuvant therapy in
      HER2-positive early stage breast cancer patients is closely related to disease-free survival
      (DFS) and overall survival (OS), which makes pCR an important evaluation indicator of
      recurrence risk. Trastuzumab combined with pertuzumab is a new standard targeted treatment
      regimen for HER2-positive early breast cancer, with overall pCR rate of 57% to 66%. However,
      there are still quite a few patients who do not reach PCR after treatment in clinical
      practice. For patients who do not reach pCR with neoadjuvant therapy, current guidelines
      recommend the use of TDM-1 for intensive treatment after surgery, but even with TDM-1, a
      significant number of patients still have recurrence or metastasis. Besides, TDM-1 is
      currently unavailable in China. Pyrotinib has been approved for HER2-positive breast cancer
      patients who have previously failed after the treatment of trastuzumab. The investigators
      intend to conduct this single-arm, single-center phase II clinical study. Patients with poor
      response to the standard neoadjuvant treatment regimen of trastuzumab combined with
      pertuzumab are enrolled. These patients receive pyrotinib to observe that whether pCR has
      been improved after the replacement of targeted treatment regimen. The investigators aim to
      explore the effect of pyrotinib in patients with poor response to standard dual-target
      neoadjuvant therapy, and further explore the improvement of neoadjuvant treatment strategy in
      HER2 positive early stage breast cancer patients.
    

Trial Arms

NameTypeDescriptionInterventions
PyrotinibExperimentalEligible patients will receive four cycles of epirubicin and cyclophosphamide combined with pyrotinib. Pyrotinib is administered orally at 400 mg daily from day 1 of the first cycle to day 21 of the fourth cycle or to the day of surgery, within 30 minutes after breakfast. Epirubicin (90 mg/m2), intravenously, every 21 days. Cyclophosphamide (600 mg/m2), intravenously, every 21 days.
  • Pyrotinib

Eligibility Criteria

        Inclusion Criteria:

          1. Female patients aged ≥ 18 years and ≤ 75 years;

          2. ECOG score 0-1;

          3. HER2-overexpressing breast cancer confirmed by immunohistochemical (IHC) analysis or
             in situ hybridization (ISH).

          4. The patient has received at least 3 cycles of neoadjuvant therapy with trastuzumab
             combined with pertuzumab and the clinical response is SD or PD (according to RECIST
             version 1.1) evaluated with breast MRI/CT/ultrasound.

          5. Known hormone receptor status (ER and PgR);

          6. The function of the main organs must meet the following requirements: 1) Blood
             routine: Neutrophil (ANC) ≥1.5 × 10^9 / L; Platelet count (PLT) ≥90 × 10^9 / L;
             Hemoglobin (Hb) ≥90 g / L; 2) Blood biochemistry: Total bilirubin (TBIL) ≤ upper limit
             of normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase
             (AST) ≤ 1.5 × ULN; Alkaline phosphatase ≤ 2.5 × ULN; Urea nitrogen (BUN) and
             creatinine (Cr) ≤ 1.5 × ULN; 3) Cardiac ultrasound: Left ventricular ejection fraction
             (LVEF) ≥55%; 4) 12-leads ECG: The QT interval corrected by Fridericia method (QTcF) is
             less than 470 msec.

          7. Voluntarily join the study and sign informed consent, with good compliance and willing
             to cooperate with follow-up.

        Exclusion Criteria:

          1. Stage IV (metastatic) breast cancer;

          2. Inflammatory breast cancer;

          3. There have been other malignant tumors in the past;

          4. Have received anthracycline, cyclophosphamide, or anti-HER2 targeted therapy other
             than trastuzumab/pertuzumab;

          5. Have participated in other clinical trials at the same time;

          6. Have undergone major surgical procedures not related to breast cancer within 4 weeks
             prior to randomization or have not fully recovered from such surgical procedures;

          7. Severe heart disease or discomfort, including but not limited to the following:

             History of diagnosis of heart failure or systolic dysfunction (LVEF <50%); High-risk
             uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate> 100 bpm,
             significant ventricular arrhythmias (such as ventricular tachycardia) or higher-level
             atrioventricular block; Angina pectoris requiring antianginal medication; Clinically
             significant heart valve disease; ECG shows transmural myocardial infarction; Poor
             hypertension control (systolic blood pressure> 180 mmHg and / or diastolic blood
             pressure> 100 mmHg);

          8. Inability to swallow, intestinal obstruction, or other factors that affect medication
             administration and absorption;

          9. People with a known history of allergies to the drugs of this study; a history of
             immunodeficiency, including a positive HIV test, or other acquired or congenital
             immunodeficiency diseases, or a history of organ transplantation;

         10. Pregnant and lactating female patients, female patients with fertility with baseline
             positive pregnancy test, or patients with fertility who are unwilling to use effective
             contraception during the entire trial and within 7 months after the last medication of
             study;

         11. Suffering from a serious concomitant disease or other comorbid condition that
             interferes with the treatment, or any other condition that the researcher considers
             unsuitable to participate in this study.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:tpCR
Time Frame:1 year
Safety Issue:
Description:the absence of invasive neoplastic cells at microscopic examination of the primary tumor and no pathological involvement of ipsilateral axillary lymph nodes at surgery

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:1 year
Safety Issue:
Description:Defined as the proportion of best overall response of either complete or partial response.
Measure:Disease free survival (DFS)
Time Frame:5 years
Safety Issue:
Description:Defined as the time from the date of surgery to the date of recurrence/metastasis or the date of death.
Measure:3-year rate of disease-free survival
Time Frame:3 years
Safety Issue:
Description:Defined as rate of 3-year disease-free survival
Measure:Event-free survival (EFS)
Time Frame:5 years
Safety Issue:
Description:Defined as the time from the date of surgery to the date of recurrence/metastasis.
Measure:Number of Participants with Adverse Events
Time Frame:1 year
Safety Issue:
Description:Defined as number of participants with adverse events related to the treatment
Measure:The quality of life
Time Frame:1 year
Safety Issue:
Description:Using EORTC (European Organization for Research and Treatment of Cancer) QLQ-BR23 scale. The minimum and maximum values are 0 and 100, respectively. Higher scores mean better outcome.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sun Yat-sen University

Last Updated

February 5, 2020