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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 : October 30, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease
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.

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Study Type : Observational
Estimated Enrollment : 250 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Actual Study Start Date : January 17, 2019
Estimated Primary Completion Date : December 9, 2020
Estimated Study Completion Date : June 7, 2023

Resource links provided by the National Library of Medicine


Group/Cohort
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



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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)


  3. 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.


Other Outcome Measures:
  1. 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).

  2. 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.

  3. 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.

  4. 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.


Biospecimen Retention:   Samples With DNA
Tissue, Plasma


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patient population with care managed in a community setting in the United States
Criteria

Inclusion Criteria:

  • Provision of written informed consent
  • Age ≥18 years old
  • Patients with histologically-confirmed diagnosis of UC and healthcare provider (HCP)-confirmed advanced UC prior to or during 1L therapy (primary histology UC; mixed histologies are allowed).

Where the 1L therapy setting is defined as:

  • Patients with no prior systemic therapy given for advanced UC; 1L is the first systemic therapy given for advanced UC
  • Patients who received neoadjuvant or adjuvant platinum-based chemotherapy with recurrence more than 12 months from the last chemotherapy dose

    • 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 available for biomarker testing (PD-L1 and tTMB).

Exclusion Criteria:

  • Patients concurrently enrolled in other clinical trials that prohibit their participation in a non-interventional study
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03788746


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

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Sponsors and Collaborators
AstraZeneca
Investigators
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Study Chair: Petros Grivas, MD University of Washington

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03788746     History of Changes
Other Study ID Numbers: D419BR00008
First Posted: December 28, 2018    Key Record Dates
Last Update Posted: October 30, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Urothelial Carcinoma
Registry
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms