Status:

ACTIVE_NOT_RECRUITING

Pyrotinib Maleate, CDK4/6 Inhibitor and Letrozole in Combination for Stage II-III TPBC: a Phase II Trial

Lead Sponsor:

Shengjing Hospital

Conditions:

Breast Cancer

Eligibility:

FEMALE

18-80 years

Phase:

PHASE2

Brief 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-...

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 part...

Eligibility Criteria

Inclusion

  • (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;
  • (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 ≥ 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

Exclusion

  • (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;
  • (15) Upon the suggestion of the investigators for other reasons

Key Trial Info

Start Date :

July 27 2020

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

December 30 2026

Estimated Enrollment :

89 Patients enrolled

Trial Details

Trial ID

NCT04486911

Start Date

July 27 2020

End Date

December 30 2026

Last Update

August 2 2022

Active Locations (1)

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Shengjing Hospital of China Medical University

Shenyang, Liaoning, China, 110004