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.
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
Interventions
Drug | Synonyms | Arms |
---|
Pyrotinib | epirubicin, cyclophosphamide | Pyrotinib |
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
Name | Type | Description | Interventions |
---|
Pyrotinib | Experimental | Eligible 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. | |
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 7, 2020