Clinical Trials /

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

NCT04486911

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: Shengjing-LCG007
  • NCT ID: NCT04486911

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Pyrotinib maleate, SHR6390, letrozolecombined treatmentPyrotinib maleate, SHR6390, letrozole

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Pyrotinib maleate, SHR6390, letrozoleExperimentalAfter 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.
  • Pyrotinib maleate, SHR6390, letrozole

Eligibility Criteria

        Inclusion Criteria:

          -  (1)Women aged > 18 years and ≤ 70 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 ≥ 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 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;

          -  (15) Upon the suggestion of the investigators for other reasons
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Total pathological complete response (tpCR)
Time Frame:1 month to 5 years after surgery
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Best overall response rate (BORR)
Time Frame:During neoadjuvant treatment (1-5 months of treatment)
Safety Issue:
Description:The proportion of patients who respond to the treatment at any study time point
Measure:Residual cancer burden (RCB)
Time Frame:1 month to 5 years after surgery
Safety Issue:
Description:RCB score is obtained according to pathological evaluation after completion of neoadjuvant treatment and surgery

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Shengjing Hospital

Trial Keywords

  • breast cancer
  • pyrotinib maleate
  • letrozole
  • CDK4/6 inhibitor

Last Updated

July 24, 2020