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临床试验/NCT03577132
NCT03577132Unknown不适用

The Efficacy of Neoadjuvant Atezolizumab Treatment in Patients With Advanced Urothelial Bladder Cancer According to the BASQ Classification

Seoul National University Hospital0 个研究点目标入组 20 人开始时间: 2018年8月1日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
不适用
入组人数
20
主要终点
objective pathological responses (pT0 change)

研究概览

简要总结

Recently, promising evidences that blocking PD-1 and PD-L1 is an efficacious way to treat advanced stage bladder cancer patients. Atezolimumab is the first PD-L1 inhibitor approved by US FDA for advanced UBC in June 2014. These novel agents will become the standard therapy for unhopeful UBC patients who fail to respond to cisplatin-based chemotherapy and finally, the first-line treatment would be changed from cisplatin-based chemotherapy to immune check point inhibitors for advanced UBC, particularly neoadjuvant setting.

Additionally, along with enormous analysis of genomic landscape of bladder cancer, a consensus was reached regarding the existence of a group of Basal-Squamous-like tumors - designated BASQ - characterized the high expression of KRT5/6 and KRT14 and low/undetectable expression of FOXA1 and GATA3. This novel molecular classification can improve the identification of optimal patient population for different treatment modalities. Specifically, luminal type and basal type may have different treatment response and prognosis after initial definitive treatment, such as neoadjuvant treatments.

However, there is no evidence for this topic, particularly the clinical efficacy of neoadjuvant PD-L1 inhibitors according to the BASQ classification in patients with advanced urothelial bladder cancer.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Parallel
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • ≥18 years of age
  • Histologically confirmed muscle-invasive urothelial carcinoma
  • Patients undergoing radical cystectomy
  • Advanced status requiring neoadjuvant systemic therapy
  • ECOG performance status score of 0 or 1
  • Adequate organ and hematologic functions
  • Available IHC data for the BASQ classification

排除标准

  • Non-urothelial carcinoma histology
  • Active autoimmune disease or inflammatory bowel disease
  • Prior severe or persistent immune-related adverse events
  • Previous exposure to anti-PD-1 or anti-PD-L1 therapy
  • Requirement for 10 mg/d of prednisone or equivalent
  • Inadequate liver, kidney function and hematologic dysfunction
  • Inoperable case, such as untreated CNS metastases
  • No available archival tumor tissue for evaluating the BASQ classification

研究组 & 干预措施

Luminal type

Experimental

Luminal type in previous transurethral resection of bladder tumor pathology. Luminal type in Immunohistochemistry (KRT5/6-KRT14-FOXA1+GATA3+)

干预措施: Neoadjuvant atezolizumab (Drug)

Basal typr

Experimental

Basal type in previous transurethral resection of bladder tumor pathology. Basal type in Immunohistochemistry (KRT5/6+KRT14+FOXA1-GATA3-)

干预措施: Neoadjuvant atezolizumab (Drug)

结局指标

主要结局

objective pathological responses (pT0 change)

时间窗: 4weeks

Final pathology of bladder after operation (radical cystectomy)

次要结局

  • progression-free survival at 1yr(1year)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Ja Hyeon Ku

Professor, MD., PHD.

Seoul National University Hospital

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