Clinical Trials /

Letrozole, Pyrotinib Combined With SHR6390 in Patients With HR+/HER2+ Relapsed/Metastatic Breast Cancer

NCT03772353

Description:

This is a single-center Ib / II study of triple targeted drug combination (aromatase inhibitor letrozole,novel HER2-targeted small molecule inhibitor pyrotinib and CDK4/6 inhibitor SHR6390) as a first or second line of therapy in patients with relapsed/metastatic hormone receptor positive and HER2-positive breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate Letrozole, Pyrotinib Combined With SHR6390 in Patients With HR+/HER2+ Relapsed/Metastatic Breast Cancer
  • Official Title: Phase Ib/II Study of Letrozole in Combination With Novel HER2-targeted Tyrosine Kinase Inhibitor Pyrotinib and CDK4/6 Inhibitor SHR6390 in Subjects With HR+/HER2+ Relapsed/Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: LORDSHIPS
  • NCT ID: NCT03772353

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
LetrozoleLetrozole in Combination with Pyrotinib and SHR6390
PyrotinibLetrozole in Combination with Pyrotinib and SHR6390
SHR6390Letrozole in Combination with Pyrotinib and SHR6390

Purpose

This is a single-center Ib / II study of triple targeted drug combination (aromatase inhibitor letrozole,novel HER2-targeted small molecule inhibitor pyrotinib and CDK4/6 inhibitor SHR6390) as a first or second line of therapy in patients with relapsed/metastatic hormone receptor positive and HER2-positive breast cancer.

Detailed Description

      This is a single-center, single arm, open-label, run-in phase Ib / roll-over phase II study
      of letrozole in combination with novel HER2-targeted tyrosine kinase Inhibitor pyrotinib and
      CDK4/6 Inhibitor SHR6390 in subjects with HR+/HER2+ relapsed or metastatic breast cancer. The
      study will enroll natural postmenopausal women, or women who have undergone bilateral
      oophorectomy.The phase Ib part of the study will determine safety and tolerability of the
      combination of letrozole, pyrotinib and SHR6390 to define that appropriate dose of SHR6390
      for phase II.The dose of letrozole and pyrotinib will be constant through the study period.
      Once the recommended regimen has been identified, subjects with the selected tumor type will
      be enrolled into expansion cohorts for the purpose of assessing efficacy and safety of the
      combination treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Letrozole in Combination with Pyrotinib and SHR6390ExperimentalDuring phase 1b part of this trial, treatment will be administered in cycles of 28 days and consist of letrozole 2.5 mg and pyrotinib 400 mgorally once daily in combination with SHR6390 (at protocol defined dose levels) po daily for 21 days followed by 7 days off. Once the recommended phase II dose (RP2D) has been determined, testing of this drug combination will be expanded in the phase II part to determine the progression-free survival (PFS) rate.
  • Letrozole
  • Pyrotinib
  • SHR6390

Eligibility Criteria

        Inclusion Criteria:

          1. Subjects voluntarily joined the study, signed informed consent, and had good
             compliance.

          2. Female patients aged 18-75 years (including cutoff value).

          3. Patients with HR+/HER2+ recurrent or metastatic breast cancer confirmed by
             histopathology in Department of Pathology, Fudan University Cancer Center

               1. HER2 positivity is defined by standard of 3+ staining by immunohistochemical
                  staining (IHC) or positive for in situ hybridization (ISH)

               2. ER or PR positive is defined as the percentage of cells positive for ER or PR
                  expression ≥ 1%

               3. Local recurrence needs to be confirmed by the physician that is unresectable

          4. At least one extracranial measurable lesion according to Response Evaluation Criteria
             in Solid Tumors (RECIST) criteria version 1.1.

          5. Natural postmenopausal women, or women who have undergone bilateral oophorectomy.

          6. Prior treatment:

               1. Previously received no more than 1prior lines of systemic chemotherapy for
                  metastatic breast cancer

               2. No more than 1prior lines of anti-HER2 treatment (alone or in combination with
                  chemotherapy or endocrine therapy) in the advanced stage

               3. No more than 1prior lines of endocrine therapy in the late stage, except for
                  those with primary or acquired resistance to letrozole or anastrozole

          7. Eastern Cooperative Oncology Group Performance Status of 0-2.

          8. Life expectancy ≥ 12 weeks.

          9. Adequate function of major organs meets the following requirements (no blood
             components and cell growth factors have been used within 14 days before
             randomization):

               1. Neutrophils ≥ 1.5×10^9/L

               2. Platelets ≥ 90×10^9/L

               3. Hemoglobin ≥ 90g/L

               4. Total bilirubin≤ 1.5 × the upper limit of normal (ULN)

               5. ALT and AST ≤ 2.5 × ULN

               6. BUN and Cr ≤ 1.5 × ULN

               7. Left ventricular ejection fraction (LVEF) ≥ 50%

               8. QTcF(Fridericia correction) ≤ 470 ms

               9. INR ≤ 1.5 × ULN,APTT≤ 1.5 × ULN

        Exclusion Criteria:

          1. The subject has untreated central nervous system (CNS) metastases.

          2. Patients who have undergone systemic, radical brain or meningeal metastasis
             (radiotherapy or surgery), but have been confirmed to have been stable for at least 4
             weeks, and who have stopped systemic hormonal therapy for more than 2 weeks without
             clinical symptoms can be included.

          3. Previously received any CDK4/6 inhibitor treatment.

          4. There are ascites, pleural effusion, pericardial effusion with clinical symptoms at
             baseline, those who need drainage, or those who have undergone drainage of serous
             effusion within 4 weeks before the first dose.

          5. Inability to swallow, intestinal obstruction or other factors affecting the
             administration and absorption of the drug.

          6. Received systemic therapy such as chemotherapy, molecular targeted therapy or other
             clinical trial drugs within 4 weeks before enrollment; received endocrine therapy
             within 2 weeks before enrollment.

          7. Patients with other malignant tumors within 5 years or at the same time( except for
             cured skin basal cell carcinoma and cervical carcinoma in situ).

          8. Have undergone major surgical procedures or significant trauma within 4 weeks prior to
             randomization, or are expected to undergo major surgery.

          9. Pregnant women, lactating female, or women of childbearing age who are unwilling to
             take effective contraceptive measures.

         10. Have a history of allergies to the drug components of this regimen.

         11. Patients with active HBV and HCV infection; stable hepatitis B after drug treatment
             (HBV virus copy number is higher than the upper limit of reference value) and cured
             hepatitis C patients (HCV virus copy number exceeds the lower limit of detection
             method).

         12. History of immunodeficiency, including HIV positive, or other acquired or congenital
             immunodeficiency disease, history of organ transplantation.

         13. History of cardiac dysfunction, include(1)angina (2)clinical significant arrythmia or
             require drug intervention (3)myocardial infarction (4)heart failure (5) other cardiac
             dysfunction (judged by the physician); any cardiac or nephric abnormal ≥ grade 2 found
             in screening.

         14. Female patients who are pregnancy, lactation or women who are of childbearing
             potential tested positive in baseline pregnancy test.

         15. Childbearing female who refuse to accept any contraception practice.

         16. Determined by the physician, any serious coexisting disease might be harmful to the
             patient's safety or avoid the patients from accomplishing the treatment(e.g serious
             hypertension, diabetes, thyroid dysfunction,active infection etc.).

         17. History of neurological or psychiatric disorders, including epilepsy or dementia.

         18. Severe infections within 4 weeks prior to first dose (eg, intravenous infusion of
             antibiotics, antifungal or antiviral drugs according to clinical protocols), or
             unexplained fever (T > 38.3 °C ) during screening or prior to first administration.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of patients in the Phase 1b part of the study with any adverse events (AE).
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Fudan University

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