An Open, Multicenter Study for the Predicted Biomarkers of CDK4/6 Inhibitors (Palbociclib) in ER-positive Metastasis Breast Cancer
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Pathway regulatory mechanism during palbociclib treatment on ER+/HER2- breast cancer.
研究概览
简要总结
This is a multi-center, observational study designed to explore the regulatory mechanism of palbociclib correlative pathways in therapeutic process of breast cancer, employing next generation sequencing (NGS) on DNA and RNA. This study also monitor the clonal evolution of genes by tracing the ctDNA.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •women aged 18-70 years old at the time of sign informed consent
- •patients diagnosed as breast cancer with evidence supporting metastatic disease, unsuitable for radical operation or radiotherapy, with no chemotherapy indication
- •full histological or cytological assessment of ER+, HER2- breast cancer
- •refractory to the most recent endocrine therapy, or progression within 12 months of endocrine therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1, no refractory within recent 2 weeks
- •patients with at least 1 measuralbe lesion; lesions will be excluded if received radiotherapy, unless had confirmed progression
- •life expectancy of 12 weeks or more
- •clinical laboratory test indicators meet the following criteria:
- •PLT≥100×10^9/L
- •ANC≥1.5×10^9/L
- •Hgb≥90 g/L
- •TBil≤1.5 ULN
- •ALT and AST ≤3 ULN
- •creatinine≤1.5 ULN or creatinine clearance rate≥50 mL/min
- •patients who signed informed consents before any projects, sampling and analysis; be available of tumor tissue biopsy and liquid biopsy; be cooperative for observation period
- •patients can swallow oral drugs
- •In addition to alopecia and stable peripheral neurotoxicity below grade 2, any clinical toxicity associated with previous treatment prior to enrollment must be restored to baseline or grade 1.
排除标准
- •no prior treatment
- •receiving treatment other than the trial 4 weeks prior to the study, or participating in another clinical study
- •unwilling to provide tissue and blood for genetic testing
- •non-resistant on endocrine therapy before treating with palbociclib
- •progress of ≥ 2nd line endocrine therapy
- •patients with advanced disease, symptoms, visceral spread, and life-threatening complications in the short term (including large uncontrollable spills [thoracic, pericardium, abdominal cavity], pulmonary lymphangitis, and liver involvement>50%)
- •patients with active, uncontrolled or symptomatic central nervous system metastases, cancerous meningitis or clinical signs suggesting pia mater disease, brain edema and/or tumor growth. Patients with a history of central nervous system metastasis or spinal cord compression, if they have received local treatment (such as radiation therapy, stereotactic surgery) and are clinically stable, they need to stop convulsions and steroids for at least 4 weeks before randomization.
- •patients received major surgery, chemotherapy, radiation therapy, or other anticancer treatments within 2 weeks prior to enrollment
- •diagnosis of any other malignant tumor, within 3 years prior to the enrollment, except adequately treated basal/squamous cell skin cancer or cervical carcinoma
- •assessed as not eligible to participate in the trial
- •infused whole blood without leukocytes removing within 120 days prior to sampling
- •during lactation or with positive blood or urine pregnancy test
研究组 & 干预措施
Palbociclib+fulvestrant
100 cases of patients with ER+, HER2- breast cancer, experienced resistance after first line endocrinotherapy, will be assigned participants into treatment regimen, including palbociclib combined with fulvestrant.
FFPE blocks/sections or fresh tumor tissues/biopsies will be obtained from the hospitals on the points before administration and since resistance appearance. The tissue will be sequenced by a pan-cancer DNA panel (500+ genes) and whole transcriptome sequencing (WTS).
5-10 ml peripheral blood will be collected from each patient on the points before administration, 1 month after treatment, every subsequent visit and resistance appearance. The liquid biopsy will be sequenced by a pan-cancer ctDNA panel (300+ genes).
The genomic characteristics of patients received resistance will be analyzed. The relevant pathway mechanisms will be identified.
干预措施: Palbociclib (Drug)
结局指标
主要结局
Pathway regulatory mechanism during palbociclib treatment on ER+/HER2- breast cancer.
时间窗: 2 year
Crosstalk patterns of genetic change processes with significant correlation with treatment of palbociclib combined endocrinotherapy, assessed by DNA and RNA sequencing.
Patterns of clonal changing on lesions during treatment of palbociclib combined endocrinotherapy.
时间窗: 2 year
The evolution patterns of genetic profiles since the begining of palbociclib combined endocrinotherapy until occurance of drug resistance obtained by collecting ctDNA variations dynamically.
次要结局
- Genetic indicators of resistance of palbociclib combined endocrinotherapy on ER+/HER2- breast cancer.(2 year)
- Genetic indicators of effect and prognosis of palbociclib combined endocrinotherapy on ER+/HER2- breast cancer.(2 year)
研究者
Li Qiao
Principal Investigator
Chinese Academy of Medical Sciences