Exploratory Study of Molecular Phenotype Changes and Personalized Treatment for Patients With Castration Resistant Prostate Cancer
试验速览
- 阶段
- 不适用
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Molecular phenotypic changes after acquired resistance of hormonal therapy
研究概览
简要总结
To explore the molecular phenotypic changes and personalized treatment in castration-resistant prostate cancer.
详细描述
This is a multi-center study to explore the molecular phenotypic changes in castration-resistant prostate cancer by histopathological,immunohistochemical and molecular analysis of cancer related genes in castration-resistant prostate cancer.After patient eligibility is determined, tumor tissue will be acquired from archival or transurethral resection or from re-biopsy specimens from patients with recurrence, visceral metastasis, bone metastases. According to the molecular phenotypic changes, personalized treatment were performed.
Participants will be screened with a full medical history and physical examination, blood and urine tests, and tumor imaging studies. The tumor specimens at diagnosis of prostate cancer should be needed for all the participants.
After assessing for the prostate specific antigen (PSA) level and the tumor molecular phenotypic features,participants will be separated into different treatment groups:
- Participants with "AR dependent" CRPC (generally with high PSA level and/or high AR expression) and with druggable gene mutations will receive Docetaxel/prednisone+Target drugs.
- Participants with "AR dependent" CRPC (generally with high PSA level and/or high AR expression) and without druggable gene mutations will receive Docetaxel/ Prednisone.
- Participants with "AR independent" CRPC (generally without AR expression and/or rapid progression with low PSA level) and with druggable gene mutations will receive Cisplatin/Etoposide+Target drugs.
- Participants with "AR independent" CRPC (generally without AR expression and/or rapid progression with low PSA level) and without druggable gene mutations will receive Cisplatin/Etoposide.
Participants with druggable gene mutations will receive the corresponding molecular targeted drugs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •18 Years and older;
- •patients with CRPC according to European Association of Urology diagnostic criteria ;
- •vital organs functions including bone marrow, heart, liver, kidney are normal;
- •complete pathological specimens including newly diagnosed with prostate cancer and disease progress to CRPC: ① biopsies or surgical specimens (tissue bank or wax block preserved specimens) at diagnosis ; ② re-biopsy specimens,transurethral prostatectomy (TURP) specimens, metastases palliative surgical specimens (tissue bank or wax block preserved specimens) after progress to CRPC; ③ amount sufficient sample for DNA extraction and quality control by up to standard (a) Sample type: None RNA degradation and pollution-free DNA samples; (b) the amount of the sample (single): ≥ 250ng (using agilent liquid platform); (c) sample concentration: ≥ 50 ng / μl (using agilent liquid platform); (d) sample purity: OD 260/280 = 1.8 ~ 2.0 );
- •Then we perform following tests when patients meet the above criteria: ①Histological analysis: Hematoxylin-eosin(HE) staining ②immunohistochemistry(IHC) staining ③ 48 carcinomas associated exon sequencing
- •After performing the above test, enter treatment group ① Docetaxel & Prednisone(DP) : with high PSA and no gene mutation; ② DP + targeted drugs: with high PSA and gene mutations; ③ cisplatin & Etoposide(EP) : low PSA and no gene mutation; ④ EP + targeted drug: Low PSA and gene mutations.
- •All patients enrolled in draw peripheral blood samples 7.5ml and detect circulating tumor cells (CTC) , monitoring efficacy.
- •Willing and able to comply with the program during the study period. 9 before entering clinical trials to provide written informed consent form, and the patient has to know you can withdraw from the study at any time in the study, and without any loss.
- •Agrees to provide blood and tissue specimens. 11 expected survival of> 6 months 12.Karnofsky performance status (KPS)> 60; Eastern Cooperative Oncology Group(ECOG) score 0-2 13 signed informed consent form
排除标准
- •other cancers
- •cognitive inability and mental abnormalities
- •other serious disease or condition
- •severe, uncontrolled internal medicine and infectious diseases
- •severe digestive disorder can not control
- •severe electrolyte imbalance
- •active disseminated intravascular coagulation
- •major organ failure, such as decompensated heart, lung, liver, kidney failure
- •peripheral neuropathy symptoms, NCI grade> Ⅱ degree
- •can not tolerate chemotherapy or refuse chemotherapy
- •using the other test drug or participate other clinical trials
- •can not oral drugs
- •receiving chemotherapy, biological therapy, or other anti-cancer medicine intervals less than 4 weeks
- •Researchers believe patients unsuitable (compliance, we should not follow-up)
研究组 & 干预措施
AR dependent CRPC
Assignment to Treatment Group based on druggable gene mutations analysis:
CRPC patients without druggable gene mutations: Docetaxel & Prednisone; CRPC patients with druggable gene mutations: DP & Targeted drugs
干预措施: Docetaxel & Prednisone (Drug)
AR dependent CRPC
Assignment to Treatment Group based on druggable gene mutations analysis:
CRPC patients without druggable gene mutations: Docetaxel & Prednisone; CRPC patients with druggable gene mutations: DP & Targeted drugs
干预措施: DP & Targeted drugs (Drug)
AR independent CRPC
Assignment to Treatment Group based on druggable gene mutations analysis:
CRPC patients without druggable gene mutations: cisplatin & Etoposide; CRPC patients with druggable gene mutations: EP & Targeted drugs
干预措施: cisplatin & Etoposide (Drug)
AR independent CRPC
Assignment to Treatment Group based on druggable gene mutations analysis:
CRPC patients without druggable gene mutations: cisplatin & Etoposide; CRPC patients with druggable gene mutations: EP & Targeted drugs
干预措施: EP & Targeted drugs (Drug)
结局指标
主要结局
Molecular phenotypic changes after acquired resistance of hormonal therapy
时间窗: 24 months
The acquired resistance criteria is based on the european criteria for castration resistant prostate cancer.The molecular phenotypic changes including the following observations:1.histopathologic analysis for rebiopsy pathology in CRPC;2.Immunohistochemical staining for androgen receptor(AR),Ki-67,cluster of differentiation 56(CD56),Syn,P53, AURKA,N-myc,retinoblastoma susceptibility(RB), E-cadherin, vimentin;3.Targeting exom sequencing by TruSeq Amplicon Cancer Panel(TSACP) including the hotspot mutation for 48 cancer related genes.
clinical progression free survival(cPFS)
时间窗: 24months
cPFS is defined as the time from the start of treatment to disease progression.
次要结局
- Overall Survival(OS)(24 months)
- The relationship between molecular phenotypic changes and OS(24 months)