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Trial record 1 of 1 for:    NCT03788746
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Prevalence of PD-L1 Expression in Patients With Advanced Urothelial Carcinoma (PREVAIL)

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ClinicalTrials.gov Identifier: NCT03788746
Recruitment Status : Recruiting
First Posted : December 28, 2018
Last Update Posted : November 16, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date November 27, 2018
First Posted Date December 28, 2018
Last Update Posted Date November 16, 2020
Actual Study Start Date January 17, 2019
Estimated Primary Completion Date December 9, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 14, 2020)
Categorization of PD-L1 results (dichotomous, high vs. low) based on pre-treatment tissue samples. [ Time Frame: 24 months ]
The proportion of advanced UC patients with biomarker PD-L1 high results will be calculated.
Original Primary Outcome Measures
 (submitted: December 23, 2018)
Categorization of PD-L1 based on pre-treatment tissue samples collected at baseline [ Time Frame: 24 months ]
Pre-treatment tumor tissue PD-L1 expression, categorized as high vs low based on an assay
Change History
Current Secondary Outcome Measures
 (submitted: April 9, 2019)
  • To assess the association of pre-treatment tumor tissue PD-L1 expression with pre-treatment tumor tissue TMB (tTMB) based on the chosen assay [ Time Frame: 24 months ]
    Assay results for pre-treatment tTMB will be assessed by pre-treatment tumor tissue PD-L1 expression status.
  • 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 [ Time Frame: 54 months ]
    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)
  • 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) [ Time Frame: 60 months ]
    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.
Original Secondary Outcome Measures
 (submitted: December 23, 2018)
  • To assess the association of pre-treatment tumor tissue PD-L1 expression with pre-treatment tumor tissue TMB (tTMB) based on the chosen assay [ Time Frame: 24 months ]
    Assay results for pre-treatment tTMB will be assessed by pre-treatment tumor tissue PD-L1 expression status.
  • 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 [ Time Frame: 60 months ]
    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)
  • 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) [ Time Frame: 60 months ]
    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.
Current Other Pre-specified Outcome Measures
 (submitted: December 23, 2018)
  • To assess the association of pre-treatment tumor tissue PD-L1 with pre-treatment bTMB [ Time Frame: 24 months ]
    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).
  • 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) [ Time Frame: 60 months ]
    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.
  • To examine the correlation between pre-treatment tTMB and bTMB values [ Time Frame: 24 months ]
    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.
  • 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 [ Time Frame: 60 months ]
    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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title 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
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.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Tissue, Plasma
Sampling Method Probability Sample
Study Population Patient population with care managed in a community setting in the United States
Condition Urothelial Carcinoma
Intervention Not Provided
Study Groups/Cohorts Patients diagnosed with advanced urothelial carcinoma
Patients with a confirmed diagnosis of advanced urothelial carcinoma, prior to or during first line therapy, who have available tumor tissue samples collected as part of standard of care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: November 13, 2020)
180
Original Estimated Enrollment
 (submitted: December 23, 2018)
250
Estimated Study Completion Date June 7, 2023
Estimated Primary Completion Date December 9, 2020   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03788746
Other Study ID Numbers D419BR00008
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor AstraZeneca
Collaborators Not Provided
Investigators
Study Chair: Petros Grivas, MD University of Washington
Study Chair: Joshua Meeks Northwestern University
PRS Account AstraZeneca
Verification Date November 2020