Clinical trial NCT03433924: An Epidemiologic Study on PD-L1 Expression Combined With Clinical Observation in the Chinese MIUBC Patients.
Official title: An Epidemiologic Study on PD-L1 Expression Combined With Clinical Observation of Initial Treatment Pattern and Overall Survival in the Chinese Muscle Invasive Urothelial Bladder Carcinoma Patients.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Urinary Bladder Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-02-15
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with a new diagnosis of MIUBC

Brief summary: The Primary Objective of this observational study is to investigate the prevalence of high PD-L1 expression in Chinese MIUBC patients.

Detailed description: The primary objective of this observational study is:

•To investigate the prevalence of high PD-L1 expression in Chinese MIUBC patients. High PD-L1 expression is defined as ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Note: PD-L1 High (\>=25% tumor cell membrane positivity for PD-L1 or 1) IF IC area \>1%: \>=25% tumor associated immune cell positivity for PD-L1; 2) If IC area=1%: 100% tumor associated immune cell positivity for PD-L1). PD-L1 Low if criteria not met for PD-L1 High.

The second objectives of this observational study are:

* To investigate the PD-L1 expression profile in TC or IC in Chinese MIUBC patients.
* To assess the concordance of PD-L1 testing results generated from the hospital labs with those from the central lab.
* To observe the initial treatment pattern for MIUBC patients in usual clinical practice in China.
* To observe 2-year OS of the Chinese MIUBC patients.

The exploratory objectives of this observational study are:

* To explore the relationship between the demographic characteristics and expression of PD-L1 and other exploratory biomarkers including immune cell (IC) subset CD8+ T cells and tumor mutation burden (TMB).
* To explore the relationship between OS and the demographic characteristics as well as the expression of biomarkers.
* To explore the relationship between PD-L1 and TMB, PD-L1 and CD8 positive T cell respectively.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years at the time of screening.
* Be able and willing to sign the informed consent form (ICF).
* Patients with histologically or cytologically documented, muscle invasive urothelial carcinoma (ie, T2 toT4, any N, any M) of bladder (see National Comprehensive Cancer Network \[NCCN\] Bladder Cancer Guidelines), who had not been previously treated with any systemic chemotherapy, radiotherapy, investigational product, or biologic therapy for cancer treatment.
* For PD-L1 testing by IHC assay, all patients were able to provide a newly acquired tumor sample within 60 days before enrollment by cystectomy, transurethral resection or biopsy. Samples with limited tumor content and fine needle aspirate specimens were not acceptable. Specimens from metastatic bone lesions were typically unacceptable unless there was a significant soft tissue component. The tumor specimen submitted to establish PD-L1 status should be of sufficient quantity to allow for PD-L1 IHC analyses and was preferred in FFPE blocks.

Exclusion Criteria:

* Prior acquiring tumor tissue samples exposure to immune-mediated therapy (including Bacillus Calmette Guerin), including but not limited to, any anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti PD L2 antibodies, therapeutic anticancer vaccines.
* Any concurrent chemotherapy, investigational product, or biologic therapy for cancer treatment. Note: Local treatment of isolated lesions, excluding target lesions, for palliative intent was acceptable (eg, local surgery or radiotherapy).

Primary outcomes:
measure: the prevalence of High PD-L1 expression in the MIUBC patients
timeFrame: Tumor tissue samples should be acquired within 60 days before the enrollment and available for testing.
Secondary outcomes:
measure: Proportion of patients with different PD-L1 expression level
timeFrame: Tumor tissue samples should be acquired within 60 days before the enrollment and available for testing.
measure: PD-L1 testing concordance between central lab and hospital labs
timeFrame: Tumor tissue samples should be acquired within 60 days before the enrollment and available for testing.
measure: Distribution percent of different treatment approaches
timeFrame: enrollment visit
measure: 2-year OS
timeFrame: From enrollment to OS, up to 2 years
Other outcomes:
measure: The prevalence of PD-L1 expression by subgroups
timeFrame: enrollment visit
measure: OS by subgroups
timeFrame: from enrollment to OS, up to 2 years
measure: Simple correlation coefficients among biomarkers
timeFrame: enrollment visit
Locations:
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Meizhou
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xiamen
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
Study officials:
affiliation: Peking University First Hospital
name: Liqun ZHOU, doctor
role: PRINCIPAL_INVESTIGATOR
References: