Breast CancerPhase 2NCT04486911
Pyrotinib Maleate, CDK4/6 Inhibitor and Letrozole in Combination for Stage II-III TPBC: a Phase II Trial
A Phase 2 study testing Pyrotinib maleate, SHR6390, letrozole in people with Breast Cancer, run by Shengjing Hospital at 1 site in China.
Trial summary
The emergence of CDK4/6 inhibitors has brought hope to breast cancer patients resistant to endocrine therapy. In the mouse model, pyrotinib maleate combined with CDK4/6 inhibitor exhibits higher anti-tumor activity than any anti-tumor drug alone. Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Pyrotinib maleate, SHR6390, letrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 89 participants
- Where
- 1 siteChina
- Study dates
- 27 Jul 2020to 30 Dec 2026
- 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 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- (1)Women aged > 18 years and ≤ 80 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
- (2) 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);
- (3) 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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- (4) Karnofsky Performance Status (KPS) Scale score ≥ 70;
- (5) The functional level of organs must meet the following requirements:
- Bone marrow function i) Absolute neutrophil count ≥ 1.5 × 109/L (no use of growth factor within 14 days) ii) Platelet count ≥ 100 × 109/L (no corrective treatment within 7 days) iii) Hemoglobin level ≥ 100 g/L (no corrective treatment within 7 days) b) Liver and kidney function i) Total bilirubin ≤1 upper limit of normal value (ULN) ii) Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3 × ULN (ALT and AST ≤ 5 × ULN in patients with liver metastasis) 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
- (6) Women who can undergo a biopsy;
- (7) Volunteers to participate in the study, provision of signed informed consent, good compliance and willingness to cooperate with follow-ups
Who cannot join
- (1) Women who have received any form of anti-tumor treatment - (chemotherapy, radiotherapy, molecular targeted therapy, or endocrine therapy);
- (2) Those who have received other anti-tumor drug treatments concurrently;
- (3) Those who have bilateral breast cancer, inflammatory breast cancer or occult breast cancer;
- (4) Those who have stage IV breast cancer;
- (5) Those who have breast cancer not histopathologically confirmed;
- (6) 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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- (7) Those who have severe dysfunction of the heart, liver, kidney, and other major organs;
- (8) There are multiple factors that affect drug administration and absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
- (9) Those who have participated in other clinical drug trials in the past 4 weeks;
- (10) 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;
- (11) 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;
- (12) 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;
- (13) 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;
- (14) A clear history of neurological or psychiatric disorders, including epilepsy or dementia;
- (15) Upon the suggestion of the investigators for other reasons
Trial locations and contacts
1 site in 1 country.
China1 site
Shengjing Hospital of China Medical University
Shenyang, Liaoning, 110004
About this study
Official title: Pyrotinib Maleate, CDK4/6 Inhibitor and Letrozole in Combination for Treatment of Stage II-III Triple-positive Breast Cancer: a Phase II Clinical Trial
The emergence of CDK4/6 inhibitors has brought hope to breast cancer patients resistant to endocrine therapy. 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. Based on above, it is hypothesized that pyrotinib maleate, CDK4/6 inhibitor SHR6390 and aromatase inhibitor letrozole in combination can provide a better neoadjuvant strategy for stage II-III triple-positive breast cancer.
Read the detailed description
This single-center, single-arm, open-label trial will include 89 patients with stage II-III triple-positive breast cancer (Simon's two-stage design). After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor SHR6390, 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.
- Conditions
- Breast Cancer
- Being tested
- Pyrotinib maleate, SHR6390, letrozole
- Keywords
- breast cancer, pyrotinib maleate, letrozole, CDK4/6 inhibitor
- 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, SHR6390, letrozoleDrug
Also called combined treatment
After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor SHR6390, 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, SHR6390, letrozole | Experimental | After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor SHR6390, 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, SHR6390, 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 (4)
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)
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
Change From Baseline of Functional Scales, Symptom Scales and Single Items in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30)
The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point(the end of cycle 2, cycle 4, and before the surgery) relative to the score at baseline .
Measured: Baseline, the end of cycle 2, cycle 4, and before the surgery
Change From Baseline of Four Functioning Scales and Four Symptom Scales in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Breast Cancer (QLQ-BR23)
EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Higher scores for symptom scales represent higher levels of symptoms/problems. For functional scales, positive change from baseline indicated deterioration in quality of life (QOL) and negative change from baseline indicated an improvement in QOL. For symptom scales, positive change from baseline indicated an improvement in quality of life (QOL) and negative change from baseline indicated a deterioration in QOL.
Measured: Baseline, the end of cycle 2, cycle 4, and before the surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2020
- Study start27 Jul 2020
- Primary completion1 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 89 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, MD, Principal investigator, Shengjing Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04486911
- Sponsor's protocol ID
- MUKDEN01
- Status last verified
- Jul 2022
- First submitted
- 21 Jul 2020
- Last updated
- 2 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- 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.
Publications
Bu J, Zhang Y, Niu N, Bi K, Sun L, Qiao X, Wang Y, Zhang Y, Jiang X, Wang D, Ma Q, Li H, Liu C. Dalpiciclib partially abrogates ER signaling activation induced by pyrotinib in HER2+HR+ breast cancer. Elife. 2023 Jan 5;12:e85246. doi: 10.7554/eLife.85246.
PubMed 36602226
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pyrotinib Maleate, CDK4/6 Inhibitor and Letrozole in Combination for Treatment of Stage II-III Triple-positive Breast Cancer: a Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT04486911
- Acronym / sponsor ID
- MUKDEN01
- Conditions
- Breast Cancer
- Keywords
- breast cancer, pyrotinib maleate, letrozole, CDK4/6 inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 89 participants (estimated)
- Lead sponsor
- Shengjing HospitalUniversity, hospital or other
- Study start
- 27 Jul 2020 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 27 Jul 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.
The emergence of CDK4/6 inhibitors has brought hope to breast cancer patients resistant to endocrine therapy. 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. Based on above, it is hypothesized that pyrotinib maleate, CDK4/6 inhibitor SHR6390 and aromatase inhibitor letrozole in combination can provide a better neoadjuvant strategy for stage II-III triple-positive breast cancer.
Detailed description
This single-center, single-arm, open-label trial will include 89 patients with stage II-III triple-positive breast cancer (Simon's two-stage design). After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor SHR6390, 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 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, SHR6390, letrozole | Experimental | Drug: Pyrotinib maleate, SHR6390, letrozoleAfter providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor SHR6390, 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 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- (1)Women aged > 18 years and ≤ 80 years meeting one of the following conditions;
- (2) 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);
- (3) 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;
- (4) Karnofsky Performance Status (KPS) Scale score ≥ 70;
- (5) The functional level of organs must meet the following requirements:
Key exclusion criteria (15 listed)
- (1) Women who have received any form of anti-tumor treatment - (chemotherapy, radiotherapy, molecular targeted therapy, or endocrine therapy);
- (2) Those who have received other anti-tumor drug treatments concurrently;
- (3) Those who have bilateral breast cancer, inflammatory breast cancer or occult breast cancer;
- (4) Those who have stage IV breast cancer;
- (5) 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, SHR6390, letrozoleAlso: combined treatmentAfter providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor SHR6390, 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, SHR6390, 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.
4 secondary outcomes
Best overall response rate (BORR)
Time frame: During neoadjuvant treatment (1-5 months of treatment)
Residual cancer burden (RCB)
Time frame: 1 month to 5 years after surgery
Change From Baseline of Functional Scales, Symptom Scales and Single Items in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30)
Time frame: Baseline, the end of cycle 2, cycle 4, and before the surgery
Change From Baseline of Four Functioning Scales and Four Symptom Scales in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Breast Cancer (QLQ-BR23)
Time frame: Baseline, the end of cycle 2, cycle 4, and before the surgery
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 2 Aug 2022.
- Derived from this study: PubMed 36602226Bu J, Zhang Y, Niu N, Bi K, Sun L, Qiao X, Wang Y, Zhang Y, Jiang X, Wang D, Ma Q, Li H, Liu C. Dalpiciclib partially abrogates ER signaling activation induced by pyrotinib in HER2+HR+ breast cancer. Elife. 2023 Jan 5;12:e85246. doi: 10.7554/eLife.85246.
- 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. This study is not recruiting at the moment.
Cai-Gang Liu, MD 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, SHR6390, 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 15 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 2 Aug 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?
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?
On the ClinicalTrials.gov record for NCT04486911, which also lists 1 linked publication.
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 2 Aug 2022.