Georgia's Online Cancer Information Center

Find A Clinical Trial

Phase III Randomized Adjuvant Study of MK-3475 (Pembrolizumab) in Muscle Invasive and Locally Advanced Urothelial Carcinoma (AMBASSADOR) versus Observation

Status
Active
Cancer Type
Bladder Cancer
Trial Phase
Phase III
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCD ID
NCT03244384
Protocol IDs
A031501 (primary)
A031501
NCI-2017-01425
A031501
Study Sponsor
Alliance for Clinical Trials in Oncology

Summary

This randomized phase III trial studies how well pembrolizumab works in treating patients with bladder cancer that has spread from where it started to nearby tissue or lymph nodes. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Objectives

PRIMARY OBJECTIVES:
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 (MK-3475) 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 MK-3475 (pembrolizumab) vs. observation.
II. To characterize the safety and tolerability of MK-3475 (pembrolizumab) when administered in the adjuvant setting in patients with muscle-invasive bladder and upper-tract urothelial carcinoma.

TERTIARY 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.
VIII. To investigate the effect of PDCD1 single-nucleotide polymorphism (SNP) rs11568821 on severe (grade 3 or higher) immune-related toxicity in the MK-3475 (pembrolizumab)-treated cohort.
IX. To investigate whether other SNPs commonly polymorphic within or near PDCD1 associate with development of MK-3475 (pembrolizumab) toxicity in the treated cohort.
X. To identify novel germline genetic markers of treatment-related toxicity through genome-wide association analysis of pembrolizumab-treated patients.
XI. To identify novel germline genetic markers that are associated with DFS and OS through genome-wide association analysis.
XII. 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 MK-3475 (pembrolizumab) vs. observation.
XIII. To compare urinary symptoms as assessed by EORTC QLQ- muscle-invasive bladder cancer module (BLM)30 between patients randomized to MK-3475 (pembrolizumab) vs. observation.
XIV. To compare patient-reported fatigue, diarrhea, and pain between patients randomized to MK-3475 (pembrolizumab) vs. observation.
XV. To compare health utilities and quality-adjusted life year (QALYs) between patients randomized to MK-3475 (pembrolizumab) vs. observation.
XVI. 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 MK-3475 (pembrolizumab) vs. observation.
XVII. To compare global quality of life, symptoms, health utilities, QALYs, and other scale scores of the three questionnaires between patients randomized to MK-3475 (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 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo observation.

After completion of study treatment, patients are followed up every 12 weeks for up 2 years, and then annually for 3 years.

Treatment Sites in Georgia

Atlanta Cancer Care - Conyers


1498 Klondike Road
Suite 106
Conyers, GA 30094
404-303-3355
www.atlantacancercare.com

Doctors:

Richard A. Carter MD

Atlanta Cancer Care - Decatur


2545 Lawrenceville Highway
Suite 300
Decatur, GA 30033
404-303-3355
www.atlantacancercare.com

Doctors:

Lijo Simpson MD

Atlanta Cancer Care - Stockbridge


7813 Spivey Station Boulevard
Suite 210
Jonesboro, GA 30236
678 466-2069
www.atlantacancercare.com

Doctors:

Gurinderjit K. Sidhu MD
Lijo Simpson MD

Georgia Cancer Specialists - CenterPointe


1100 Johnson Ferry Road
Suite 600
Sandy Springs, GA 30342
404-256-4777 ext 9242
www.gacancer.com

Doctors:

Rodolfo E. Bordoni MD
Pradeep C. Jolly MD

Georgia Cancer Specialists - Macon-Coliseum


308 Coliseum Drive
Suite 120
Macon, GA 31217
478-745-6130 x8152
www.gacancer.com

Doctors:

Cheryl F. Jones MD
Premila Malhotra MD
Georgia CORE

 

Hearts and Minds Dedicated to Improving Cancer Care

Georgia CORE is a public-private partnership that creates collaboration among the state’s cancer organizations and institutions to connect more Georgians to quality, personalized cancer care. We welcome you to this one-of-a-kind online information center for all things related to cancer and survivorship care in Georgia.