Breast Cancer InvasivePhase 2NCT04398914
Pyrotinib, Trastuzumab, Pertuzumab and Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer
A Phase 2 study testing Pyrotinib, Trastuzumab and Pertuzumab in people with Breast Cancer Invasive, run by Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Breast Cancer Invasive
- What is being tested?
- Pyrotinib, Trastuzumab and Pertuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 216 participants
- Where
- 1 siteChina
- Study dates
- 30 May 2020to 30 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
China1 site
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, 200025
About this study
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
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.
Read the 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.
- Conditions
- Breast Cancer Invasive
- Being tested
- Pyrotinib, Trastuzumab, Pertuzumab, Nab-paclitaxel, EC chemotherapy
- Keywords
- HER2-positive, Stage II-III
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyrotinibDrug
Pyrotinib 400 mg taken orally everyday, every 3 weeks, for 4 cycles.
TrastuzumabDrug
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
PertuzumabDrug
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-paclitaxelDrug
Nab-paclitaxel 100mg/m2 by intravenous (IV) infusion on day1, day8 and day15, every 3 weeks, for 4 cycles.
EC chemotherapyDrug
Epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 by intravenous (IV) infusion every 3 weeks for 4 cycles (Cycles 5-8)
Physician's choiceDrug
Physician decided chemotherapy for 0-4 cycles.
T-DM1Drug
T-DM1 IV infusion in 3-week cycles. 3.6 mg/kg by intravenous (IV) infusion every 3 weeks for 14 cycles
SurgeryProcedure or surgery
All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.
| Study group | Role | What they receive |
|---|---|---|
| Pyrotinib, trastuzumab, pertuzmab and paclitaxel | Experimental | 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. Receives: Drug: Pyrotinib; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Nab-paclitaxel; Drug: EC chemotherapy; Drug: Physician's choice; Drug: T-DM1; Procedure: Surgery |
| Trastuzumab, pertuzmab and paclitaxel | Active comparator | 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. Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Nab-paclitaxel; Drug: EC chemotherapy; Drug: Physician's choice; Drug: T-DM1; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After completion of 4 cycles of neoadjuvant therapy. The duration of one treatment cycle is 21 days
Secondary outcomes (5)
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.
Measured: After completion of 4 cycles of neoadjuvant therapy The duration of one treatment cycle is 21 days. at the time of surgery
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.
Measured: Cycle 1-4. 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.
Measured: From Baseline to EFS event or date last known to be alive and event-free (up to 5 years)
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.
Measured: From surgery to DFS event or date last known to be alive and event-free (up to 5 years)
Overall survival (OS)
OS was defined as the time from randomization to death from any cause.
Measured: From Baseline to OS event or date last known to be alive (up to 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2020
- Study start30 May 2020
- Primary completion30 Dec 2022 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer InvasiveStudies of the same condition, open and under way.
- More trials run by Shanghai Jiao Tong University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 216 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Jiao Tong University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Jiangsu HengRui Medicine Co., Ltd.
- Responsible party
- Principal investigator, Kunwei Shen, Shanghai Jiao Tong University School of Medicine
- Investigators
- Kunwei Shen, MD,PhD, Study chair, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04398914
- Sponsor's protocol ID
- RJBC2001
- Status last verified
- Mar 2022
- First submitted
- 19 May 2020
- Last updated
- 31 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04398914
- Acronym / sponsor ID
- RJBC2001
- Conditions
- Breast Cancer Invasive
- Keywords
- HER2-positive, Stage II-III
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 216 participants (estimated)
- Lead sponsor
- Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Collaborators
- Jiangsu HengRui Medicine Co., Ltd.
- Study start
- 30 May 2020 (actual)
- Primary completion
- 30 Dec 2022 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 22 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pyrotinib, trastuzumab, pertuzmab and paclitaxel | Experimental | Drug: Pyrotinib, Drug: Trastuzumab, Drug: Pertuzumab, Drug: Nab-paclitaxel, Drug: EC chemotherapy, Drug: Physician's choice, Drug: T-DM1, Procedure: SurgeryPrior 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. |
| Trastuzumab, pertuzmab and paclitaxel | Active comparator | Drug: Trastuzumab, Drug: Pertuzumab, Drug: Nab-paclitaxel, Drug: EC chemotherapy, Drug: Physician's choice, Drug: T-DM1, Procedure: SurgeryPrior 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PyrotinibPyrotinib 400 mg taken orally everyday, every 3 weeks, for 4 cycles. | Drug | Pyrotinib, trastuzumab, pertuzmab and paclitaxel |
| TrastuzumabTrastuzumab 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 | Pyrotinib, trastuzumab, pertuzmab and paclitaxel, Trastuzumab, pertuzmab and paclitaxel |
| PertuzumabPertuzumab 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 | Pyrotinib, trastuzumab, pertuzmab and paclitaxel, Trastuzumab, pertuzmab and paclitaxel |
| Nab-paclitaxelNab-paclitaxel 100mg/m2 by intravenous (IV) infusion on day1, day8 and day15, every 3 weeks, for 4 cycles. | Drug | Pyrotinib, trastuzumab, pertuzmab and paclitaxel, Trastuzumab, pertuzmab and paclitaxel |
| EC chemotherapyEpirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 by intravenous (IV) infusion every 3 weeks for 4 cycles (Cycles 5-8) | Drug | Pyrotinib, trastuzumab, pertuzmab and paclitaxel, Trastuzumab, pertuzmab and paclitaxel |
| Physician's choicePhysician decided chemotherapy for 0-4 cycles. | Drug | Pyrotinib, trastuzumab, pertuzmab and paclitaxel, Trastuzumab, pertuzmab and paclitaxel |
| T-DM1T-DM1 IV infusion in 3-week cycles. 3.6 mg/kg by intravenous (IV) infusion every 3 weeks for 14 cycles | Drug | Pyrotinib, trastuzumab, pertuzmab and paclitaxel, Trastuzumab, pertuzmab and paclitaxel |
| SurgeryAll participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated. | Procedure or surgery | Pyrotinib, trastuzumab, pertuzmab and paclitaxel, Trastuzumab, pertuzmab and paclitaxel |
Primary outcome
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.
5 secondary outcomes
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
Clinical response
Time frame: 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)
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)
Overall survival (OS)
Time frame: From Baseline to OS event or date last known to be alive (up to 5 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kunwei Shen, MD,PhD study chair
Ruijin Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pyrotinib, Trastuzumab and Pertuzumab in people with Breast Cancer Invasive, run by Shanghai Jiao Tong University School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 31 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2022.