- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04398914
Pyrotinib, Trastuzumab, Pertuzumab and Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer
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 Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Shanghai
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Shanghai, Shanghai, China, 200025
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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:
|
All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.
Pyrotinib 400 mg taken orally everyday, every 3 weeks, for 4 cycles.
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 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
Nab-paclitaxel 100mg/m2 by intravenous (IV) infusion on day1, day8 and day15, every 3 weeks, for 4 cycles.
Epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 by intravenous (IV) infusion every 3 weeks for 4 cycles (Cycles 5-8)
Physician decided chemotherapy for 0-4 cycles.
T-DM1 IV infusion in 3-week cycles.
3.6 mg/kg by intravenous (IV) infusion every 3 weeks for 14 cycles
|
Active Comparator: Trastuzumab, pertuzmab and paclitaxel
Prior to surgery: trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days). After surgery:
|
All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.
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 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
Nab-paclitaxel 100mg/m2 by intravenous (IV) infusion on day1, day8 and day15, every 3 weeks, for 4 cycles.
Epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 by intravenous (IV) infusion every 3 weeks for 4 cycles (Cycles 5-8)
Physician decided chemotherapy for 0-4 cycles.
T-DM1 IV infusion in 3-week cycles.
3.6 mg/kg by intravenous (IV) infusion every 3 weeks for 14 cycles
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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After completion of 4 cycles of neoadjuvant therapy. The duration of one treatment cycle is 21 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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After completion of 4 cycles of neoadjuvant therapy The duration of one treatment cycle is 21 days. at the time of surgery
|
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.
|
Cycle 1-4. The duration of one treatment cycle is 21 days.
|
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.
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From Baseline to EFS event or date last known to be alive and event-free (up to 5 years)
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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)
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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.
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From surgery to DFS event or date last known to be alive and event-free (up to 5 years)
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Overall survival (OS)
Time Frame: From Baseline to OS event or date last known to be alive (up to 5 years)
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OS was defined as the time from randomization to death from any cause.
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From Baseline to OS event or date last known to be alive (up to 5 years)
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With At Least One Adverse Event During Treatment Period
Time Frame: From randomization to 30 days after completion of study treatment
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The percentage of participants who experienced at least one adverse event during the neoadjuvant period, surgery, adjuvant treatment period.
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From randomization to 30 days after completion of study treatment
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Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Kunwei Shen, MD,PhD, Ruijin Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Paclitaxel
- Trastuzumab
- Pertuzumab
Other Study ID Numbers
- RJBC2001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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