Combination treatment for stage II-III triple-positive breast cancer

Pyrotinib Maleate, Trastuzumab, SHR6390(Dalpiciclib) and Letrozole in Combination for Neoadjuvant Treatment of Stage II-III TPBC

This study is testing a new combination treatment for women with stage II-III triple-positive breast cancer to see if it helps shrink tumors before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Shengjing Hospital (Academic / other)
• Drugs / interventions: chemotherapy, trastuzumab, pyrotinib, lapatinib
• Locations: 1 site (Shenyang, Liaoning)
• Trial ID: NCT05228951 on ClinicalTrials.gov

What this trial studies

This multi-center, single-arm, open-label trial aims to evaluate the effectiveness of a combination treatment involving pyrotinib maleate, the CDK4/6 inhibitor dalpiciclib, trastuzumab, and letrozole in women with stage II-III triple-positive breast cancer. Participants will receive the treatment for five cycles, with effectiveness assessed through MRI every two cycles. If the treatment shows effectiveness, participants will undergo surgical treatment within four weeks after completing the therapy. The study focuses on patients who have specific hormone receptor-positive breast cancer characteristics.

Who should consider this trial

Good fit: Ideal candidates are women aged 18 to 75 with stage II-III triple-positive breast cancer.

Not a fit: Patients with non-triple-positive breast cancer or those who do not meet the hormonal receptor criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with triple-positive breast cancer.

How similar studies have performed: Previous studies have shown promising results with similar combination therapies in treating breast cancer, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Women aged≥18 years and ≤75 years meeting one of the following conditions;

   1. Those previously receiving ovariectomy, or aged ≥60 years
   2. 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
   3. 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;
4. Karnofsky Performance Status (KPS) Scale score ≥70;
5. The functional level of organs must meet the following requirements:

   a) 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
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.

Exclusion Criteria:

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;
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. Upon the suggestion of the investigators for other reasons

Where this trial is running

Shenyang, Liaoning

• Shengjing Hospital of China Medical University — Shenyang, Liaoning, China (Recruiting)

Study contacts

• Principal investigator: Cai-Gang Liu, PHD — Shengjing Hospital
• Study coordinator: Nan Niu, MD

Conditions Breast Cancer; breast cancer; pyrotinib maleate; letrozole; SHR6390; trastuzumab; dalpiciclib