Breast CancerPhase 2NCT05228951
Pyrotinib Maleate, Trastuzumab, SHR6390 and Letrozole in Combination for Stage II-III TPBC
A Phase 2 study testing Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozole in people with Breast Cancer, run by Shengjing Hospital at 1 site in China.
Trial summary
NOAH study confirmed that trastuzumab combined with chemotherapy can significantly improve PCR compared with chemotherapy alone, and established the status of trastuzumab as a new adjuvant targeted therapy. The emergence of CDK4/6 inhibitors has brought hope to breast cancer patients resistant to endocrine therapy. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- 10 Feb 2022to 31 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women aged≥18 years and ≤75 years meeting one of the following conditions;
- Those previously receiving ovariectomy, or aged ≥60 years
- Those aged < 60 years who have had 12 consecutive months of amenorrhoea without any pathological or physical causes, and have postmenopausal E2 and follicle stimulating hormone (FSH) levels
- Premenopausal or perimenopausal women who are willing to receive LHRH agonist treatment during the study period
- Women who have breast cancer histopathologically confirmed by positive estrogen receptor (ER; >10%), positive progesterone receptor (PR; >1%), and positive human epidermal growth factor receptor 2 (HER2) according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) guideline. ER, PR and HER2 will be assessed by immunohistochemistry (IHC) on harvested tissue. ER, PR and HER2 will be considered positive if the IHC result is positive (score 3+), or the IHC result is positive (2+) and in situ hybridization (ISH) amplification rate (≥2.0);
- Women having stage II-III breast cancer diagnosed based on AJCC cancer staging system (8th edition) who will be admitted because of breast cancer for the first time;
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- Karnofsky Performance Status (KPS) Scale score ≥70;
- The functional level of organs must meet the following requirements:
- Bone marrow function i) Absolute neutrophil count（ANC）≥1.5×109/L (no use of growth factor within 14 days) ii) Platelet count（PLT）≥100×109/L (no corrective treatment within 7 days) iii) Hemoglobin level（Hb）≥100 g/L (no corrective treatment within 7 days) b) Liver and kidney function i) Total bilirubin（TBIL）≤1.5 upper limit of normal value (ULN) ii) Alanine transaminase (ALT) and aspartate transaminase (AST) ≤3×ULN iii) Blood urea nitrogen (BUN) and creatinine ≤1.5×ULN and creatinine clearance≥50 mL/min (Cockcroft-Gault formula); c) Color Doppler echocardiography: Left ventricular ejection fraction ≥50% d) 12-lead electrocardiography: QTc interval ≤480 ms
- Women who can undergo a biopsy;
- Volunteers to participate in the study, provision of signed informed consent, good compliance and willingness to cooperate with follow-ups.
Who cannot join
- Women who have received any form of anti-tumor treatment - (chemotherapy, radiotherapy, molecular targeted therapy, or endocrine therapy);
- Those who have received other anti-tumor drug treatments concurrently;
- Those who have bilateral breast cancer, inflammatory breast cancer or occult breast cancer;
- Those who have stage IV breast cancer;
- Those who have breast cancer not histopathologically confirmed;
- Those who have other malignant tumors (with the exception of healed cervical carcinoma in situ) occurring in the past 5 years;
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- Those who have severe dysfunction of the heart, liver, kidney, and other major organs;
- There are multiple factors that affect drug administration and absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
- Those who have participated in other clinical drug trials in the past 4 weeks;
- Those who are known to have a history of allergy to the component of study drugs; those who have a history of immunodeficiency, including positive detection of human immunodeficiency virus, hepatitis C virus, active hepatitis B or other acquired, congenital immunodeficiency diseases, or organ transplantation;
- Those who had suffered from any heart disease, including arrhythmia which requires drug treatment or is of clinical significance; myocardial infarction; heart failure; and any other heart disease judged by the investigator as unsuitable for this trial;
- Pregnant and lactating women; fertile women who provide positive results of baseline pregnancy test; women of childbearing age who are unwilling to take effective contraceptive measures during the whole study period;
- If the accompanying diseases (including, but not limited to, severe hypertension, severe diabetes, and active infection, which cannot be controlled by drugs) that would be a potential hazard to participant's health, or affect the completion of the study as per investigator's judgement;
- A clear history of neurological or psychiatric disorders, including epilepsy or dementia. Upon the suggestion of the investigators for other reasons
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shengjing Hospital of China Medical University
Shenyang, Liaoning, 110004
Nan Niu, MD, +8618940256668, niunannancy@163.com
Cai-Gang Liu, PHD
About this study
Official title: Pyrotinib Maleate, Trastuzumab, SHR6390(Dalpiciclib) and Letrozole in Combination for Neoadjuvant Treatment of Stage II-III TPBC
NOAH study confirmed that trastuzumab combined with chemotherapy can significantly improve PCR compared with chemotherapy alone, and established the status of trastuzumab as a new adjuvant targeted therapy. The emergence of CDK4/6 inhibitors has brought hope to breast cancer patients resistant to endocrine therapy. studies have shown that pyrotinib maleate combined with CDK4/6 inhibitor can significantly inhibit the proliferation of HER2 positive breast cancer cell lines, reduce the activation of pAKT and pHER3, inhibit cell arrest in G0-G1 phase, and increase cell apoptosis. In the mouse model, pyrotinib maleate combined with CDK4/6 inhibitor exhibits higher anti-tumor activity than any anti-tumor drug alone. Moreover, the toxicity of the combined therapy does not increase compared with monotherapy. This provides a good preclinical model for the treatment of breast cancer by pyrotinib maleate combined with CDK4/6 inhibitor.
In addition, NeoALTTO study、CALGB 40601 study、NSABP B-41 study confirmed that the clinical efficacy of lapatinib combined with trastuzumab combined chemotherapy was better than that of lapatinib or trastuzumab single target treatment group. Therefore, it is envisaged that the combination of pyrotinib maleate and dalpiciclib combined with letrozole on the basis of adding new trastuzumab to treat triple positive breast cancer will further improve the curative effect.
In conclusion, we believe that pyrotinib maleate combined with trastuzumab, dalpiciclib and letrozole can provide better strategies for neoadjuvant therapy in patients with II-III three positive breast cancer.
Read the detailed description
This multi-center, single-arm, open-label trial will include 12 patients with stage II-III triple-positive breast cancer. After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor dalpiciclib, trastuzumab，and letrozole. The effectiveness of the combined treatment will be evaluated by MRI every two treatment cycles. If the disease progresses, the participant will withdraw from the trial. If the combined treatment has identified effectiveness, the participant will undergo surgical treatment within 4 weeks (over 2 weeks) after termination of the five treatment cycles.
- Conditions
- Breast Cancer
- Being tested
- Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozole
- Keywords
- breast cancer, pyrotinib maleate, letrozole, SHR6390, trastuzumab, dalpiciclib
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozoleDrug
Also called combined treatment
After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor dalpiciclib, trastuzumab and letrozole. The effectiveness of the combined treatment will be evaluated by MRI every two treatment cycles. If the disease progresses, the participant will withdraw from the trial. If the combined treatment has identified effectiveness, the participant will undergo surgical treatment within 4 weeks (over 2 weeks) after termination of the neoadjuvant treatment. The patients will be followed up for 5 years.
| Study group | Role | What they receive |
|---|---|---|
| Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozole | Experimental | After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor dalpiciclib, trastuzumab and letrozole. The effectiveness of the combined treatment will be evaluated by MRI every two treatment cycles. If the disease progresses, the participant will withdraw from the trial. If the combined treatment has identified effectiveness, the participant will undergo surgical treatment within 4 weeks (over 2 weeks) after termination of the neoadjuvant treatment. The patients will be followed up for 5 years. Receives: Drug: Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total pathological complete response (tpCR)
tpCR is defined as the absence of residual invasive cancer on resected breast specimen and the sampled regional lymph nodes as shown by hematoxylin-eosin staining after completion of the neoadjuvant treatment
Measured: 1 month to 5 years after surgery
Secondary outcomes (6)
Best overall response rate (BORR)
The proportion of patients who respond to the treatment at any study time point
Measured: During neoadjuvant treatment(1-5 months of treatment)
Breast pathologic complete response (bpCR)
There was no invasive carcinoma in the primary breast lesions (ypT0-is)
Measured: 1 month to 5 years after surgery
Residual cancer burden (RCB)
RCB score is obtained according to pathological evaluation after completion of neoadjuvant treatment and surgery
Measured: 1 month to 5 years after surgery
Overall survival (OS)
It refers to the length of time from the start of treatment to the death of the patient
Measured: Within 5 years after surgery
Disease-free survival (DFS)
It refers to the length of time from the start of medication after enrollment to the death of the patient because of the recurrence, distant metastasis of the disease, invasive contralateral breast cancer, or any other cause
Measured: Within 5 years after surgery
Subject safety
Number of Adverse Events using NCI CTCAE 5.0
Measured: From signing the informed consent to 28 days after last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2022
- Study start10 Feb 2022
- Primary completion31 Dec 2022 (estimated)
- Study completion31 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 CancerStudies of the same condition, open and under way.
- More trials run by Shengjing HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- single arm study
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shengjing Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Caigang Liu, Shengjing Hospital
- Investigators
- Cai-Gang Liu, PHD, Principal investigator, Shengjing Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05228951
- Sponsor's protocol ID
- Shengjing-LCG011
- Status last verified
- Sep 2022
- First submitted
- 13 Jan 2022
- Last updated
- 13 Sep 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Findings from this study will indicate whether pyrotinib maleate, CDK4/6 inhibitor SHR6390 and letrozole for treatment of stage II-III triple-positive breast cancer is safe and effective
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pyrotinib Maleate, Trastuzumab, SHR6390(Dalpiciclib) and Letrozole in Combination for Neoadjuvant Treatment of Stage II-III TPBC
- ClinicalTrials.gov ID
- NCT05228951
- Acronym / sponsor ID
- Shengjing-LCG011
- Conditions
- Breast Cancer
- Keywords
- breast cancer, pyrotinib maleate, letrozole, SHR6390, trastuzumab, dalpiciclib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Shengjing HospitalUniversity, hospital or other
- Study start
- 10 Feb 2022 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 8 Feb 2022 (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.
NOAH study confirmed that trastuzumab combined with chemotherapy can significantly improve PCR compared with chemotherapy alone, and established the status of trastuzumab as a new adjuvant targeted therapy. The emergence of CDK4/6 inhibitors has brought hope to breast cancer patients resistant to endocrine therapy. studies have shown that pyrotinib maleate combined with CDK4/6 inhibitor can significantly inhibit the proliferation of HER2 positive breast cancer cell lines, reduce the activation of pAKT and pHER3, inhibit cell arrest in G0-G1 phase, and increase cell apoptosis. In the mouse model, pyrotinib maleate combined with CDK4/6 inhibitor exhibits higher anti-tumor activity than any anti-tumor drug alone. Moreover, the toxicity of the combined therapy does not increase compared with monotherapy. This provides a good preclinical model for the treatment of breast cancer by pyrotinib maleate combined with CDK4/6 inhibitor.
In addition, NeoALTTO study、CALGB 40601 study、NSABP B-41 study confirmed that the clinical efficacy of lapatinib combined with trastuzumab combined chemotherapy was better than that of lapatinib or trastuzumab single target treatment group. Therefore, it is envisaged that the combination of pyrotinib maleate and dalpiciclib combined with letrozole on the basis of adding new trastuzumab to treat triple positive breast cancer will further improve the curative effect.
In conclusion, we believe that pyrotinib maleate combined with trastuzumab, dalpiciclib and letrozole can provide better strategies for neoadjuvant therapy in patients with II-III three positive breast cancer.
Detailed description
This multi-center, single-arm, open-label trial will include 12 patients with stage II-III triple-positive breast cancer. After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor dalpiciclib, trastuzumab，and letrozole. The effectiveness of the combined treatment will be evaluated by MRI every two treatment cycles. If the disease progresses, the participant will withdraw from the trial. If the combined treatment has identified effectiveness, the participant will undergo surgical treatment within 4 weeks (over 2 weeks) after termination of the five treatment cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single arm study
| Arm | Type | Receives |
|---|---|---|
| Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozole | Experimental | Drug: Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozoleAfter providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor dalpiciclib, trastuzumab and letrozole. The effectiveness of the combined treatment will be evaluated by MRI every two treatment cycles. If the disease progresses, the participant will withdraw from the trial. If the combined treatment has identified effectiveness, the participant will undergo surgical treatment within 4 weeks (over 2 weeks) after termination of the neoadjuvant treatment. The patients will be followed up for 5 years. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Women aged≥18 years and ≤75 years meeting one of the following conditions;
- Women who have breast cancer histopathologically confirmed by positive estrogen receptor (ER; >10%), positive progesterone receptor (PR; >1%), and positive human epidermal growth factor receptor 2 (HER2) according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) guideline. ER, PR and HER2 will be assessed by immunohistochemistry (IHC) on harvested tissue. ER, PR and HER2 will be considered positive if the IHC result is positive (score 3+), or the IHC result is positive (2+) and in situ hybridization (ISH) amplification rate (≥2.0);
- Women having stage II-III breast cancer diagnosed based on AJCC cancer staging system (8th edition) who will be admitted because of breast cancer for the first time;
- Karnofsky Performance Status (KPS) Scale score ≥70;
- The functional level of organs must meet the following requirements:
Key exclusion criteria (14 listed)
- Women who have received any form of anti-tumor treatment - (chemotherapy, radiotherapy, molecular targeted therapy, or endocrine therapy);
- Those who have received other anti-tumor drug treatments concurrently;
- Those who have bilateral breast cancer, inflammatory breast cancer or occult breast cancer;
- Those who have stage IV breast cancer;
- Those who have breast cancer not histopathologically confirmed;
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 |
|---|---|---|
| Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozoleAlso: combined treatmentAfter providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor dalpiciclib, trastuzumab and letrozole. The effectiveness of the combined treatment will be evaluated by MRI every two treatment cycles. If the disease progresses, the participant will withdraw from the trial. If the combined treatment has identified effectiveness, the participant will undergo surgical treatment within 4 weeks (over 2 weeks) after termination of the neoadjuvant treatment. The patients will be followed up for 5 years. | Drug | Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozole |
Primary outcome
Total pathological complete response (tpCR)
Time frame: 1 month to 5 years after surgery
tpCR is defined as the absence of residual invasive cancer on resected breast specimen and the sampled regional lymph nodes as shown by hematoxylin-eosin staining after completion of the neoadjuvant treatment
6 secondary outcomes
Best overall response rate (BORR)
Time frame: During neoadjuvant treatment(1-5 months of treatment)
Breast pathologic complete response (bpCR)
Time frame: 1 month to 5 years after surgery
Residual cancer burden (RCB)
Time frame: 1 month to 5 years after surgery
Overall survival (OS)
Time frame: Within 5 years after surgery
Disease-free survival (DFS)
Time frame: Within 5 years after surgery
Subject safety
Time frame: From signing the informed consent to 28 days after last dose
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 13 Sep 2022.
- Individual participant dataSharing planned: Yes. Findings from this study will indicate whether pyrotinib maleate, CDK4/6 inhibitor SHR6390 and letrozole for treatment of stage II-III triple-positive breast cancer is safe and effective
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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.
Cai-Gang Liu, PHD principal investigator
Shengjing 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 maleate, dalpiciclib, Trastuzumab, letrozole in people with Breast Cancer, run by Shengjing Hospital 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 11 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 13 Sep 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?
Contact Nan Niu, MD (+8618940256668, niunannancy@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total pathological complete response (tpCR) (time frame: 1 month to 5 years after surgery). 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 13 Sep 2022.