Prevalence of PD-L1 Expression in Patients With Advanced Urothelial Carcinoma (PREVAIL)
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| ClinicalTrials.gov Identifier: NCT03788746 |
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Recruitment Status :
Active, not recruiting
First Posted : December 28, 2018
Last Update Posted : May 24, 2022
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Sponsor:
AstraZeneca
Information provided by (Responsible Party):
AstraZeneca
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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 |
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| Urothelial Carcinoma |
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 |
| Actual Enrollment : | 180 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 |
| Actual Primary Completion Date : | February 5, 2021 |
| Estimated Study Completion Date : | June 7, 2023 |
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| Group/Cohort |
|---|
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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
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Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
Other Outcome Measures:
- 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.
Biospecimen Retention: Samples With DNA
Tissue, Plasma
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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
- 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
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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
Locations
Show 58 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
| Study Chair: | Petros Grivas, MD | University of Washington | |
| Study Chair: | Joshua Meeks | Northwestern University |
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT03788746 |
| Other Study ID Numbers: |
D419BR00008 |
| First Posted: | December 28, 2018 Key Record Dates |
| Last Update Posted: | May 24, 2022 |
| Last Verified: | May 2022 |
| Individual Participant Data (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 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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Urothelial Carcinoma Registry |
Additional relevant MeSH terms:
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Carcinoma Carcinoma, Transitional Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms |