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

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ClinicalTrials.gov Identifier: NCT04398914
Recruitment Status : Recruiting
First Posted : May 22, 2020
Last Update Posted : July 8, 2020
Sponsor:
Collaborator:
Jiangsu HengRui Medicine Co., Ltd.
Information provided by (Responsible Party):
Kunwei Shen, Shanghai Jiao Tong University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Invasive Drug: Pyrotinib Drug: Trastuzumab Drug: Pertuzumab Drug: Nab-paclitaxel Drug: EC chemotherapy Drug: Physician's choice Drug: T-DM1 Procedure: Surgery Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 216 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 30, 2020
Estimated Primary Completion Date : December 30, 2022
Estimated Study Completion Date : December 30, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Pyrotinib, trastuzumab, pertuzmab and paclitaxel

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.
Drug: Pyrotinib
Pyrotinib 400 mg taken orally everyday, every 3 weeks, for 4 cycles.

Drug: Trastuzumab

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


Drug: Pertuzumab

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


Drug: Nab-paclitaxel
Nab-paclitaxel 100mg/m2 by intravenous (IV) infusion on day1, day8 and day15, every 3 weeks, for 4 cycles.

Drug: EC chemotherapy
Epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 by intravenous (IV) infusion every 3 weeks for 4 cycles (Cycles 5-8)

Drug: Physician's choice
Physician decided chemotherapy for 0-4 cycles.

Drug: T-DM1
T-DM1 IV infusion in 3-week cycles. 3.6 mg/kg by intravenous (IV) infusion every 3 weeks for 14 cycles

Procedure: Surgery
All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.

Active Comparator: Trastuzumab, pertuzmab and paclitaxel

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.
Drug: Trastuzumab

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


Drug: Pertuzumab

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


Drug: Nab-paclitaxel
Nab-paclitaxel 100mg/m2 by intravenous (IV) infusion on day1, day8 and day15, every 3 weeks, for 4 cycles.

Drug: EC chemotherapy
Epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 by intravenous (IV) infusion every 3 weeks for 4 cycles (Cycles 5-8)

Drug: Physician's choice
Physician decided chemotherapy for 0-4 cycles.

Drug: T-DM1
T-DM1 IV infusion in 3-week cycles. 3.6 mg/kg by intravenous (IV) infusion every 3 weeks for 14 cycles

Procedure: Surgery
All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.




Primary Outcome Measures :
  1. Percentage of Participants With Total Pathologic Complete Response (tpCR) [ Time Frame: After completion of 4 cycles of neoadjuvant therapy. The duration of one treatment cycle is 21 days ]
    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 :
  1. Percentage of Participants With Breast Pathologic Complete Response (bpCR) [ Time Frame: After completion of 4 cycles of neoadjuvant therapy The duration of one treatment cycle is 21 days. at the time of surgery ]
    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.

  2. Clinical response [ Time Frame: Cycle 1-4. The duration of one treatment cycle is 21 days. ]
    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.

  3. Event-free survival (EFS) [ Time Frame: From Baseline to EFS event or date last known to be alive and event-free (up to 5 years) ]
    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.

  4. Disease-free survival (DFS) [ Time Frame: From surgery to DFS event or date last known to be alive and event-free (up to 5 years) ]
    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.

  5. Overall survival (OS) [ Time Frame: From Baseline to OS event or date last known to be alive (up to 5 years) ]
    OS was defined as the time from randomization to death from any cause.


Other Outcome Measures:
  1. Percentage of Participants With At Least One Adverse Event During Treatment Period [ Time Frame: From randomization to 30 days after completion of study treatment ]
    The percentage of participants who experienced at least one adverse event during the neoadjuvant period, surgery, adjuvant treatment period.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04398914


Contacts
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Contact: Jiahui Huang, MD +8615121007182 hjh3269@163.com
Contact: Xiaosong Chen, MD chenxiaosong0156@163.com

Locations
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China, Shanghai
Ruijin Hospital, Shanghai Jiaotong University School of Medicine Recruiting
Shanghai, Shanghai, China, 200025
Contact: Jiahui Huang       hjh3269@163.com   
Sponsors and Collaborators
Shanghai Jiao Tong University School of Medicine
Jiangsu HengRui Medicine Co., Ltd.
Investigators
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Study Chair: Kunwei Shen, MD,PhD Ruijin Hospital
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Responsible Party: Kunwei Shen, Professor, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier: NCT04398914    
Other Study ID Numbers: RJBC2001
First Posted: May 22, 2020    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kunwei Shen, Shanghai Jiao Tong University School of Medicine:
HER2-positive
Stage II-III
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Trastuzumab
Pertuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological