Testing MK-3475 (Pembrolizumab) After Surgery for Localized Muscle-Invasive Bladder Cancer and Locally Advanced Urothelial Cancer (AMBASSADOR)
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ClinicalTrials.gov Identifier: NCT03244384 |
Recruitment Status :
Active, not recruiting
First Posted : August 9, 2017
Last Update Posted : May 20, 2024
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Tracking Information | |||||
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First Submitted Date ICMJE | August 7, 2017 | ||||
First Posted Date ICMJE | August 9, 2017 | ||||
Last Update Posted Date | May 20, 2024 | ||||
Actual Study Start Date ICMJE | November 3, 2017 | ||||
Estimated Primary Completion Date | June 1, 2025 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Testing MK-3475 (Pembrolizumab) After Surgery for Localized Muscle-Invasive Bladder Cancer and Locally Advanced Urothelial Cancer | ||||
Official Title ICMJE | Phase III Randomized Adjuvant Study of Pembrolizumab in muScle invaSive and locAlly aDvanced urOthelial caRcinoma (AMBASSADOR) Versus Observation | ||||
Brief Summary | This phase III trial studies how well pembrolizumab works in treating patients with bladder cancer that has spread into the deep muscle of the bladder wall (muscle-invasive) or urothelial cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced). Monoclonal antibodies recognizing and blocking checkpoint molecules can enhance the patient's immune response and therefore help fight cancer. Pembrolizumab is one of the monoclonal antibodies that block the PD-1 axis and can interfere with the ability of tumor cells to grow. | ||||
Detailed Description | DUAL PRIMARY OBJECTIVE: I. To determine disease free survival (DFS) and overall survival (OS) in all patients with muscle-invasive bladder and upper-tract urothelial carcinoma treated with adjuvant pembrolizumab versus (vs.) observation. SECONDARY OBJECTIVES: I. To determine DFS and OS in PD-L1 positive and negative patients with muscle-invasive bladder and upper-tract urothelial carcinoma treated with adjuvant pembrolizumab vs. observation. II. To characterize the safety and tolerability of pembrolizumab when administered in the adjuvant setting in patients with muscle-invasive bladder and upper-tract urothelial carcinoma. CORRELATIVE SCIENCE OBJECTIVES: I. To determine if the 12 immune gene signatures are associated with OS and DFS. II. To determine if tumor molecular subtype is associated with OS and DFS. III. To investigate whether the diversity of T-cell receptor (TCR) clonotypes is associated with OS and DFS. IV. To investigate whether persistence of TCR clonotypes is associated with OS and DFS. V. To determine if tumor burden and neoantigen burden are associated with OS and DFS. VI. To determine if HLA subtypes are associated with OS and DFS. VII. To conduct exploratory analyses regarding the association of plasma HGF and VEGF levels with IL-10 and IL-17 and OS and DFS and between treated and untreated patients. PHARMACOGENOMIC STUDY OBJECTIVES: I. To investigate the effect of PDCD1 single-nucleotide polymorphism (SNP) rs11568821 on severe (grade 3 or higher) immune-related toxicity in the pembrolizumab-treated cohort. II. To investigate whether other SNPs commonly polymorphic within or near PDCD1 associate with development of pembrolizumab toxicity in the treated cohort. III. To identify novel germline genetic markers of treatment-related toxicity through genome-wide association analysis of pembrolizumab-treated patients. IV. To identify novel germline genetic markers that are associated with DFS and OS through genome-wide association analysis. QUALITY OF LIFE CORRELATIVE STUDY OBJECTIVES: I. To compare health-related quality of life (HRQL) as assessed by the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-core (C)30 between patients randomized to pembrolizumab vs. observation. II. To compare urinary symptoms as assessed by EORTC QLQ- muscle-invasive bladder cancer module (BLM)30 between patients randomized to pembrolizumab vs. observation. III. To compare patient-reported fatigue, diarrhea, and pain between patients randomized to pembrolizumab vs. observation. IV. To compare health utilities and quality-adjusted life year (QALYs) between patients randomized to pembrolizumab vs. observation. V. To compare other scale scores of the EORTC QLQ-C30, EORTC QLQ-BLM30, and European Quality of Life 5 Dimensions 5 Levels (EQ5D-5L) between patients randomized to pembrolizumab vs. observation. VI. To compare global quality of life, symptoms, health utilities, QALYs, and other scale scores of the three questionnaires between patients randomized to pembrolizumab vs. observation within subgroups defined by each of the stratification factors. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a computed tomography (CT) scan, CT urography, and/or magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo a cystoscopy and blood sample collection during screening and on study. ARM B: Patients undergo observation. Patients undergo a CT scan, CT urography, and/or MRI throughout the trial. Patients may also undergo a cystoscopy and blood sample collection during screening and on study. After completion of study treatment, patients are followed up every 12 weeks for up 2 years, and then annually for 3 years. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 3 | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Active, not recruiting | ||||
Estimated Enrollment ICMJE |
739 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | June 1, 2025 | ||||
Estimated Primary Completion Date | June 1, 2025 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | Guam, United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03244384 | ||||
Other Study ID Numbers ICMJE | NCI-2017-01425 NCI-2017-01425 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) A031501 A031501 ( Other Identifier: Alliance for Clinical Trials in Oncology ) A031501 ( Other Identifier: CTEP ) U10CA180821 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Current Responsible Party | National Cancer Institute (NCI) | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | ||||
Verification Date | May 2024 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |