Clinical trial NCT04398914: Pyrotinib, Trastuzumab, Pertuzumab and Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer
Official title: A Randomised, Multicenter, Open-label, Phase II Study Evaluating Pyrotinib Plus Trastuzumab, Pertuzumab and Nab-paclitaxel as Neoadjuvant Therapy in Early Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2 - Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer Invasive
Keywords: HER2-positive
Stage II-III
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2020-05-22
Enrollment: 216
Sex: ALL
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: This study aims to evaluate the efficacy and safety of pyrotinib in combination with trastuzumab, pertuzumab and nab-paclitaxel as neoadjuvant therapy in early stage or locally advanced HER2-positive breast cancer.

Detailed description: The study evaluate the pathological complete response rate, event-free survival, disease-free survival, overall survival and safety of pyrotinib in combination with trastuzumab, pertuzumab and nab-paclitaxel as neoadjuvant therapy in early stage or locally advanced HER2-positive breast cancer. Patients will receive 4 cycles of pyrotinib in combination with trastuzumab, pertuzumab and nab-paclitaxel or 4 cycles of trastuzumab, pertuzumab and nab-paclitaxel as neoadjuvant therapy, then undergo surgery, then receive adjuvant chemotherapy and targeted therapy according to pathologic response and physician's choice.

Eligibility criteria: Inclusion Criteria:

* With signed consent
* Histologically confirmed invasive breast carcinoma with a primary tumor size of no less than (≥) 2 centimeters (cm) by standard local assessment technique
* Breast cancer stage at presentation: stage II-III
* HER2-positive breast cancer defined as 3+ score by immunohistochemistry in \> 10 percent (%) of immunoreactive cells or HER2 gene amplification by in situ hybridization
* Known hormone receptor status (estrogen receptor and/or progesterone receptor)
* Eastern Cooperative Oncology Group Performance Status equal to or less than (\<=) 1
* Baseline left ventricular ejection fracture \>= 50% measured by echocardiography
* Willing to use highly effective form of nonhormonal contraception while on study and for 7 months after end of study treatment for female with fertility or male
* Willing to obey the study protocol

Exclusion Criteria:

* Stage IV disease
* Previous anti-cancer therapy or radiotherapy for any malignancy
* History of other malignancy within 5 years prior to screening, except for appropriately-treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, ,Stage I uterine cancer or thyroid papillary microcarcinoma
* Concurrent anti-cancer treatment in another investigational trial, including hormone therapy, bisphosphonate therapy, or immunotherapy
* Major surgical procedure unrelated to breast cancer within 4 weeks prior to randomization or from which the participant has not fully recovered
* Serious cardiac illness or medical condition
* Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
* Any abnormalities in liver, kidney or hematologic function laboratory tests immediately prior to randomization
* Sensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol
* Not able to swallow the drug
* Pregnant or lactating
* Positive serum or urine pregnancy test or above mentioned tests cannot be achieved for women with fertility

Primary outcomes:
measure: Percentage of Participants With Total Pathologic Complete Response (tpCR)
timeFrame: After completion of 4 cycles of neoadjuvant therapy. The duration of one treatment cycle is 21 days
Secondary outcomes:
measure: Percentage of Participants With Breast Pathologic Complete Response (bpCR)
timeFrame: After completion of 4 cycles of neoadjuvant therapy The duration of one treatment cycle is 21 days. at the time of surgery
measure: Clinical response
timeFrame: Cycle 1-4. The duration of one treatment cycle is 21 days.
measure: Event-free survival (EFS)
timeFrame: From Baseline to EFS event or date last known to be alive and event-free (up to 5 years)
measure: Disease-free survival (DFS)
timeFrame: From surgery to DFS event or date last known to be alive and event-free (up to 5 years)
measure: Overall survival (OS)
timeFrame: From Baseline to OS event or date last known to be alive (up to 5 years)
Other outcomes:
measure: Percentage of Participants With At Least One Adverse Event During Treatment Period
timeFrame: From randomization to 30 days after completion of study treatment
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Kunwei Shen, MD,PhD
role: STUDY_CHAIR
References: