Status:
UNKNOWN
Pyrotinib, Dalpiciclib(SHR6390) and Endocrine Therapy in Subjects With Dual-receptor Positive(ER+/HER2+) Advanced Breast Cancer
Lead Sponsor:
Fudan University
Collaborating Sponsors:
Jiangsu HengRui Medicine Co., Ltd.
Conditions:
Breast Cancer
Eligibility:
FEMALE
18-75 years
Phase:
PHASE1
PHASE2
Brief Summary
This is a single-center Ib / II study of triple targeted drug combination (endocrine therapy，novel HER2-targeted small molecule inhibitor pyrotinib and CDK4/6 inhibitor dalpiciclib(SHR6390) ) as a fir...
Detailed Description
This is a single-center, single arm, open-label, run-in phase Ib / roll-over phase II study of endocrine therapy in combination with novel human epidermal growth factor receptor-2(HER2)-targeted tyros...
Eligibility Criteria
Inclusion
- Subjects voluntarily joined the study, signed informed consent, and had good compliance.
- Postmenopausal or premenopausal perimenopausal female patients aged ≥ 18 years and ≤ 75 years old,Meet one of the following:
- Previous bilateral oophorectomy, or age ≥ 60 years; or Age \<60, natural postmenopausal state (defined as regular months for at least 12 consecutive months After spontaneous cessation and no other pathological or physiological reasons),E2 and FSH in menopause Post-level; or
- Pre-menopausal or perimenopausal female patients can also be included, but must be willing to receive treatment with LHRH agonists;
- Patients with HR+/HER2+ recurrent or metastatic breast cancer confirmed by histopathology
- HER2 positivity is defined by standard of 3+ staining by immunohistochemical staining (IHC) or positive for in situ hybridization (ISH)
- Estrogen receptor(ER) or Progesterone receptor(PR) positive is defined as the percentage of cells positive for ER or PR expression ≥ 1%
- Local recurrence needs to be confirmed by the physician that is unresectable
- At least one extracranial measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.
- Prior treatment:
- Previously received no more than 1 prior lines of systemic treatment with trastuzumab regimen for repetitive metastatic diabetes \[including anti-HER2 ADC, subsequent meaning is the same\]
- The early stage includes trastuzumab-containing regimen treatment， or trastuzumab-containing regimen that relapses more than 1 year after the end of adjuvant treatment, and subsequent treatment is included as the first-line anti-HER2 treatment;
- The first-line treatment fails with the trastuzumab-containing regimen, or the trastuzumab-containing regimen recurs during the adjuvant treatment or relapses within 1 year after the adjuvant treatment ends, the follow-up treatment will be included as the second-line anti-HER2 treatment;
- Have not received anti-HER2 TKI treatment before or received but did not prove that the treatment failed;
- Past endocrine therapy has not proven resistance to aromatase inhibitors (definition of resistance: recurrence during or within 1 year after treatment with adjuvant aromatase inhibitors, received aromatase inhibitors in the recurrence and metastasis stage and disease progression), follow-up Letrozole is selected for endocrine therapy. Past endocrine therapy has aromatase inhibitor resistance, and follow-up endocrine therapy is fulvestrant.
- Eastern Cooperative Oncology Group Performance Status of 0-1.
- Life expectancy ≥ 12 weeks.
- Adequate function of major organs meets the following requirements (no blood components and cell growth factors have been used within 14 days before randomization):
- Neutrophils ≥ 1.5×10\^9/L
- Platelets ≥ 90×10\^9/L
- Hemoglobin ≥ 90g/L
- Total bilirubin≤ 1.5 × the upper limit of normal (ULN)
- ALT and AST ≤ 2.5 × ULN
- BUN and Cr ≤ 1.5 × ULN
- Left ventricular ejection fraction (LVEF) ≥ 50%
- QTcF(Fridericia correction) ≤ 470 ms
- International normalized ratio(INR)≤1.5 × ULN，activated partial thromboplastin time(APTT) ≤ 1.5 × ULN
Exclusion
- Meningeal metastasis or active brain parenchymal metastasis. Patients with clinically stable brain parenchymal metastases can be included, including asymptomatic brain metastases that have not received local treatment; or patients who have previously received central nervous system metastasis therapy (radiotherapy or surgery), if imaging confirms that stability has been maintained for at least 4 weeks , and have stopped symptomatic treatment (including hormones and mannitol, etc.) for more than 2 weeks
- Previously received any CDK4/6 inhibitor treatment.
- 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.
- Inability to swallow, intestinal obstruction or other factors affecting the administration and absorption of the drug.
- 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.
- 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).
- Have undergone major surgical procedures or significant trauma within 4 weeks prior to randomization, or are expected to undergo major surgery.
- Pregnant women, lactating female, or women of childbearing age who are unwilling to take effective contraceptive measures.
- Have a history of allergies to the drug components of this regimen.
- 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).
- History of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, history of organ transplantation.
- 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.
- Female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test.
- Childbearing female who refuse to accept any contraception practice.
- 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.).
- History of neurological or psychiatric disorders, including epilepsy or dementia.
- 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.
Key Trial Info
Start Date :
May 12 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 10 2025
Estimated Enrollment :
59 Patients enrolled
Trial Details
Trial ID
NCT03772353
Start Date
May 12 2019
End Date
December 10 2025
Last Update
March 7 2023
Active Locations (1)
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1
Fudan University Shanghai Cancer Center
Shanghai, China, 200032