Prevalence of PD-L1 Expression in Patients With Advanced Urothelial Carcinoma

Urothelial Carcinoma Clinical Trial

— PREVAIL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03788746
• Other study ID #: D419BR00008
• Status: Completed
• Start date: January 17, 2019
• Est. completion date: May 25, 2023

Study information

• Verified date: February 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: May 25, 2023
• Est. primary completion date: January 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Locations

Country	Name	City	State
United States	Research Site	Albany	New York
United States	Research Site	Augusta	Georgia
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Berkeley Heights	New Jersey
United States	Research Site	Boca Raton	Florida
United States	Research Site	Brewer	Maine
United States	Research Site	Bridgeton	Missouri
United States	Research Site	Cedar Rapids	Iowa
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Denver	Colorado
United States	Research Site	Duluth	Minnesota
United States	Research Site	East Brunswick	New Jersey
United States	Research Site	Englewood	New Jersey
United States	Research Site	Englewood	Colorado
United States	Research Site	Freehold	New Jersey
United States	Research Site	Geneva	Illinois
United States	Research Site	Glendale	California
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Greenville	North Carolina
United States	Research Site	Greenwood	Indiana
United States	Research Site	Hartford	Connecticut
United States	Research Site	Harvey	Illinois
United States	Research Site	Hialeah	Florida
United States	Research Site	Jacksonville	Florida
United States	Research Site	Johnson City	New York
United States	Research Site	Kansas City	Kansas
United States	Research Site	Kettering	Ohio
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Lafayette	Indiana
United States	Research Site	Lake Barrington	Illinois
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lewiston	Maine
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Little Silver	New Jersey
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Monterey	California
United States	Research Site	Mount Laurel	New Jersey
United States	Research Site	Muncie	Indiana
United States	Research Site	Myrtle Beach	South Carolina
United States	Research Site	Naperville	Illinois
United States	Research Site	Nashville	Tennessee
United States	Research Site	Olympia	Washington
United States	Research Site	Port Jefferson Station	New York
United States	Research Site	Renton	Washington
United States	Research Site	Roswell	Georgia
United States	Research Site	Saint Cloud	Minnesota
United States	Research Site	Santa Rosa	California
United States	Research Site	Seattle	Washington
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Stamford	Connecticut
United States	Research Site	Tacoma	Washington
United States	Research Site	Temple	Texas
United States	Research Site	The Woodlands	Texas
United States	Research Site	Virginia Beach	Virginia
United States	Research Site	Waterloo	Iowa
United States	Research Site	Wenatchee	Washington
United States	Research Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To assess the association of pre-treatment tumor tissue PD-L1 with pre-treatment bTMB	bTMB levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Results for TMB can range from 0 (non-shedder) to very high values >50 mut/Mb (no maximum has been determined). The results for pre-treatment bTMB will be presented by PD-L1 results (high vs low).	24 months
Other	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)	ctDNA levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. VAF is the relative frequency of alleles at a particular locus in a population, expressed as a percentage, ranging from 0.3% to 100%. Changes in ctDNA levels at 3 points of sample testing will be assessed.	60 months
Other	To examine the correlation between pre-treatment tTMB and bTMB values	bTMB levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Assay results for pre-treatment tTMB will be assessed by pre-treatment bTMB results.	24 months
Other	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	bTMB and ctDNA levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Objective response, PFS, and OS (defined in secondary outcome measures) will be assessed by the following: changes to ctDNA levels (VAFs) at 3 timepoints (defined above); and pre-treatment tTMB assay results compared with pre-treatment bTMB assay results.	60 months
Primary	Categorization of PD-L1 results (dichotomous, high vs. low) based on pre-treatment tissue samples.	The proportion of advanced UC patients with biomarker PD-L1 high results will be calculated.	24 months
Secondary	To assess the association of pre-treatment tumor tissue PD-L1 expression with pre-treatment tumor tissue TMB (tTMB) based on the chosen assay	Assay results for pre-treatment tTMB will be assessed by pre-treatment tumor tissue PD-L1 expression status.	24 months
Secondary	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	1L advanced UC treatment patterns (such as regimen/agents used, start (first dose) and stop (last dose) dates, reasons for cis/carboplatin ineligibility) will be collected.; Objective Response: complete or partial response based on healthcare provider (HCP) assessment; Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria highly recommended Progression: evidence malignancy has become worse or spreads in the body (based on HCP assessment).; Objective response and survival endpoints (overall, stratified by PD-L1 expression [high vs. low] including the following: ORR: The proportion of patients with a complete or partial response based on HCP assessment; PFS: The time from the start of 1L advanced UC treatment until progression or death (any cause); and OS: The time from start of 1L advanced UC treatment until death (any cause)	54 months
Secondary	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)	Objective response, PFS, and OS (defined above) will be stratified by pre-treatment tumor tissue PD-L1 expression, and among patients treated with anti-PD-L1/PD-1 or chemotherapy or other.	60 months

External Links

•   Redacted CSR synopsis