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Pyrotinib, Trastuzumab, Pertuzumab and Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer

Primary Purpose

Breast Cancer Invasive

Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Pyrotinib
Trastuzumab
Pertuzumab
Nab-paclitaxel
EC chemotherapy
Physician's choice
T-DM1
Surgery
Sponsored by
Shanghai Jiao Tong University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer Invasive focused on measuring HER2-positive, Stage II-III

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Pyrotinib, trastuzumab, pertuzmab and paclitaxel

Trastuzumab, pertuzmab and paclitaxel

Arm Description

Prior to surgery: pyrotinib, trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days). After surgery： if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles. if tpCR: chemotherapy 0-4 cycles according to physician's choice, followed with pertuzumab and trastuzumab up to 1 year total.

Prior to surgery: trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days). After surgery： if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles. if tpCR: chemotherapy 0-4 cycles according to physician's choice; followed with pertuzumab and trastuzumab up to 1 year total.

Outcomes

Primary Outcome Measures

Percentage of Participants With Total Pathologic Complete Response (tpCR)
tpCR is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer [AJCC] staging system).The duration of one treatment cycle is 21 days.

Secondary Outcome Measures

Percentage of Participants With Breast Pathologic Complete Response (bpCR)
bpCR is defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is, in accordance with current AJCC staging system).The duration of one treatment cycle is 21 days.
Clinical response
Percentage of Participants With Complete Response, Partial Response, Stable Disease, or Progressive Disease During Cycles 1-4, According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The duration of one treatment cycle is 21 days.
Event-free survival (EFS)
EFS is defined as the time from randomization to the first documentation of one of the following events: Disease progression (before surgery) as determined by the investigator with use of RECIST v1.1 Any evidence of contralateral disease in situ was not identified as progressive disease; Disease recurrence (local, regional, distant, or contralateral) after surgery; Death from any cause.
Disease-free survival (DFS)
DFS was defined as the time from first date of no disease (i.e., date of surgery) to first documentation of one of the following events: Disease recurrence (local, regional, distant, or contralateral) after surgery. Any evidence of contralateral disease in situ was not identified as disease recurrence; Death from any cause.
Overall survival (OS)
OS was defined as the time from randomization to death from any cause.

Full Information

First Posted
May 19, 2020
Last Updated
March 28, 2022
Sponsor
Shanghai Jiao Tong University School of Medicine
Collaborators
Jiangsu HengRui Medicine Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04398914
Brief Title
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

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 30, 2020 (Actual)
Primary Completion Date
December 30, 2022 (Anticipated)
Study Completion Date
December 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Jiao Tong University School of Medicine
Collaborators
Jiangsu HengRui Medicine Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer Invasive
Keywords
HER2-positive, Stage II-III

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
216 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pyrotinib, trastuzumab, pertuzmab and paclitaxel
Arm Type
Experimental
Arm Description
Prior to surgery: pyrotinib, trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days). After surgery： if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles. if tpCR: chemotherapy 0-4 cycles according to physician's choice, followed with pertuzumab and trastuzumab up to 1 year total.
Arm Title
Trastuzumab, pertuzmab and paclitaxel
Arm Type
Active Comparator
Arm Description
Prior to surgery: trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days). After surgery： if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles. if tpCR: chemotherapy 0-4 cycles according to physician's choice; followed with pertuzumab and trastuzumab up to 1 year total.
Intervention Type
Drug
Intervention Name(s)
Pyrotinib
Intervention Description
Pyrotinib 400 mg taken orally everyday, every 3 weeks, for 4 cycles.
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Intervention Description
Trastuzumab IV infusion in 3-week cycles. Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4. Adjuvant treatment: 8 mg/kg loading dose, followed by 6 mg/kg for remaining cycles till completion of 1 year trastuzumab
Intervention Type
Drug
Intervention Name(s)
Pertuzumab
Intervention Description
Pertuzumab IV infusion in 3-week cycles. Neoadjuvant treatment: 840 milligrams (mg) loading dose for Cycle 1, followed by 420 mg for Cycles 2-4. Adjuvant treatment: 840 mg loading dose, followed by 420mg for remaining cycles till completion of 1 year pertuzumab
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Intervention Description
Nab-paclitaxel 100mg/m2 by intravenous (IV) infusion on day1, day8 and day15, every 3 weeks, for 4 cycles.
Intervention Type
Drug
Intervention Name(s)
EC chemotherapy
Intervention Description
Epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 by intravenous (IV) infusion every 3 weeks for 4 cycles (Cycles 5-8)
Intervention Type
Drug
Intervention Name(s)
Physician's choice
Intervention Description
Physician decided chemotherapy for 0-4 cycles.
Intervention Type
Drug
Intervention Name(s)
T-DM1
Intervention Description
T-DM1 IV infusion in 3-week cycles. 3.6 mg/kg by intravenous (IV) infusion every 3 weeks for 14 cycles
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.
Primary Outcome Measure Information:
Title
Percentage of Participants With Total Pathologic Complete Response (tpCR)
Description
tpCR is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer [AJCC] staging system).The duration of one treatment cycle is 21 days.
Time Frame
After completion of 4 cycles of neoadjuvant therapy. The duration of one treatment cycle is 21 days
Secondary Outcome Measure Information:
Title
Percentage of Participants With Breast Pathologic Complete Response (bpCR)
Description
bpCR is defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is, in accordance with current AJCC staging system).The duration of one treatment cycle is 21 days.
Time Frame
After completion of 4 cycles of neoadjuvant therapy The duration of one treatment cycle is 21 days. at the time of surgery
Title
Clinical response
Description
Percentage of Participants With Complete Response, Partial Response, Stable Disease, or Progressive Disease During Cycles 1-4, According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The duration of one treatment cycle is 21 days.
Time Frame
Cycle 1-4. The duration of one treatment cycle is 21 days.
Title
Event-free survival (EFS)
Description
EFS is defined as the time from randomization to the first documentation of one of the following events: Disease progression (before surgery) as determined by the investigator with use of RECIST v1.1 Any evidence of contralateral disease in situ was not identified as progressive disease; Disease recurrence (local, regional, distant, or contralateral) after surgery; Death from any cause.
Time Frame
From Baseline to EFS event or date last known to be alive and event-free (up to 5 years)
Title
Disease-free survival (DFS)
Description
DFS was defined as the time from first date of no disease (i.e., date of surgery) to first documentation of one of the following events: Disease recurrence (local, regional, distant, or contralateral) after surgery. Any evidence of contralateral disease in situ was not identified as disease recurrence; Death from any cause.
Time Frame
From surgery to DFS event or date last known to be alive and event-free (up to 5 years)
Title
Overall survival (OS)
Description
OS was defined as the time from randomization to death from any cause.
Time Frame
From Baseline to OS event or date last known to be alive (up to 5 years)
Other Pre-specified Outcome Measures:
Title
Percentage of Participants With At Least One Adverse Event During Treatment Period
Description
The percentage of participants who experienced at least one adverse event during the neoadjuvant period, surgery, adjuvant treatment period.
Time Frame
From randomization to 30 days after completion of study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kunwei Shen, MD,PhD
Organizational Affiliation
Ruijin Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pyrotinib, Trastuzumab, Pertuzumab and Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer

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