Clinical trial NCT03788746: Prevalence of PD-L1 Expression in Patients With Advanced Urothelial Carcinoma
Official title: A Prospective, Non-Interventional Study to Assess the Prevalence of PD-L1 Expression in the First-Line Setting of Locally Advanced/Unresectable or Metastatic Urothelial Carcinoma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Urothelial Carcinoma
Keywords: Urothelial Carcinoma
Registry
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-12-28
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient population with care managed in a community setting in the United States

Brief summary: The purpose of this study is to assess the prevalence of pre-treatment tumor tissue PD-L1 expression in patients diagnosed with advanced urothelial carcinoma.

Detailed description: Advanced urothelial carcinoma (UC) (locally advanced/unresectable or metastatic UC) is a fatal disease with 5-year survival rate of 5%. The most frequently studied diagnostic for advanced UC is the programmed death-ligand 1 (PD-L1) protein expression in tumor tissue. A better understanding of PD-L1 expression in a "real world" setting could help understand its clinical utility in the management and decision making in advanced UC and clinical trial design

Eligibility criteria: Inclusion Criteria:

* Provision of written informed consent
* Age ≥18 years old
* Patient must have advanced UC confirmed by their HCP; histologically- confirmed diagnosis of UC an dHCP-confirmed advanced UC.
* Patient must be either currently receiving 1L systemic treatment for their advanced UC or will be starting 1L systemic treatment (i.e. "newly diagnosed" advanced UC; 1L therapy is defined as the first systemic therapy given for advanced UC).
* Patient remains eligible for the study if they received neoadjuvant or adjuvant platinum-based chemotherapy if their recurrence was more than 12 months after their last chemotherapy dose.
* Radio-sensitizing chemotherapy as part of chemoradiation is NOT counted as neoadjuvant or adjuvant chemotherapy; thus, the 12-month interval mention above does not apply, and the patient would be eligible
* Patients with available tumor tissue sample (fresh or archival - up to 3 years old) that was collected as part of SoC any time prior to 1L treatment for advanced UC with a target of 18 slides (7 minimum) available for biomarker testing (PD-L1 and tTMB). Already prepared slides must have been cut within 6 months prior to PD-L1 testing.

Exclusion Criteria:

* Patients concurrently enrolled in other clinical trials that prohibit their participation in a non-interventional study
* Patient has resectable localized UC and has refused surgery
* Patients with history of non-urothelial active malignancy that completed therapy within 2 years from study enrollment except:

  * Any resected in situ carcinoma or non-melanoma skin cancer
  * Localized (early stage) cancer treated with curative intent (without evidence of recurrence and intent for further therapy) and in which no systemic therapy was indicated

Primary outcomes:
measure: Categorization of PD-L1 results (dichotomous, high vs. low) based on pre-treatment tissue samples.
timeFrame: 24 months
Secondary outcomes:
measure: To assess the association of pre-treatment tumor tissue PD-L1 expression with pre-treatment tumor tissue TMB (tTMB) based on the chosen assay
timeFrame: 24 months
measure: To describe the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) as well as treatment patterns in the 1L setting of advanced UC
timeFrame: 54 months
measure: To assess the association between pre-treatment tumor tissue PD-L1 expression with objective response, PFS, and OS among treated patients (anti PD-L1/PD-1, chemotherapy, other)
timeFrame: 60 months
Other outcomes:
measure: To assess the association of pre-treatment tumor tissue PD-L1 with pre-treatment bTMB
timeFrame: 24 months
measure: To assess changes in ctDNA levels (variant allele fractions [VAFs]) at 3 points of sample testing: (1) Before starting 1L treatment (pre-treatment) (2) before initiating treatment on day 1 of cycle 3, and (3) at the time of progression (if applicable)
timeFrame: 60 months
measure: To examine the correlation between pre-treatment tTMB and bTMB values
timeFrame: 24 months
measure: To assess the prognostic value of pre-treatment and changes to ctDNA levels, and pre-treatment tTMB compared to bTMB, for outcomes of ORR, PFS, and OS
timeFrame: 60 months
Locations:
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Glendale
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Monterey
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Englewood
country: United States
facility: Research Site
state: Colorado
city: Hartford
country: United States
facility: Research Site
state: Connecticut
city: Stamford
country: United States
facility: Research Site
state: Connecticut
city: Boca Raton
country: United States
facility: Research Site
state: Florida
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Roswell
country: United States
facility: Research Site
state: Georgia
city: Geneva
country: United States
facility: Research Site
state: Illinois
city: Harvey
country: United States
facility: Research Site
state: Illinois
city: Lake Barrington
country: United States
facility: Research Site
state: Illinois
city: Naperville
country: United States
facility: Research Site
state: Illinois
city: Greenwood
country: United States
facility: Research Site
state: Indiana
city: Lafayette
country: United States
facility: Research Site
state: Indiana
city: Muncie
country: United States
facility: Research Site
state: Indiana
city: Cedar Rapids
country: United States
facility: Research Site
state: Iowa
city: Waterloo
country: United States
facility: Research Site
state: Iowa
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Brewer
country: United States
facility: Research Site
state: Maine
city: Lewiston
country: United States
facility: Research Site
state: Maine
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: Duluth
country: United States
facility: Research Site
state: Minnesota
city: Saint Cloud
country: United States
facility: Research Site
state: Minnesota
city: Bridgeton
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Berkeley Heights
country: United States
facility: Research Site
state: New Jersey
city: East Brunswick
country: United States
facility: Research Site
state: New Jersey
city: Englewood
country: United States
facility: Research Site
state: New Jersey
city: Freehold
country: United States
facility: Research Site
state: New Jersey
city: Little Silver
country: United States
facility: Research Site
state: New Jersey
city: Mount Laurel
country: United States
facility: Research Site
state: New Jersey
city: Albany
country: United States
facility: Research Site
state: New York
city: Johnson City
country: United States
facility: Research Site
state: New York
city: Port Jefferson Station
country: United States
facility: Research Site
state: New York
city: Greenville
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Kettering
country: United States
facility: Research Site
state: Ohio
city: Myrtle Beach
country: United States
facility: Research Site
state: South Carolina
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Temple
country: United States
facility: Research Site
state: Texas
city: The Woodlands
country: United States
facility: Research Site
state: Texas
city: Virginia Beach
country: United States
facility: Research Site
state: Virginia
city: Olympia
country: United States
facility: Research Site
state: Washington
city: Renton
country: United States
facility: Research Site
state: Washington
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Wenatchee
country: United States
facility: Research Site
state: Washington
Study officials:
affiliation: University of Washington
name: Petros Grivas, MD
role: STUDY_CHAIR
affiliation: Northwestern University
name: Joshua Meeks
role: STUDY_CHAIR
References: