Localized Renal Pelvis and Ureter Urothelial CarcinomaPhase 3AMBASSADORNCT03244384
Testing MK-3475 (Pembrolizumab) After Surgery for Localized Muscle-Invasive Bladder Cancer and Locally Advanced Urothelial Cancer
A Phase 3 study testing Biospecimen Collection, Clinical Observation and Computed Tomography in people with Localized Renal Pelvis and Ureter Urothelial Carcinoma and Locally Advanced Bladder Urothelial Carcinoma, run by National Cancer Institute (NCI) at 914 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Localized Renal Pelvis and Ureter Urothelial Carcinoma, Locally Advanced Bladder Urothelial Carcinoma, Locally Advanced Renal Pelvis and Ureter Urothelial Carcinoma
- What is being tested?
- Biospecimen Collection, Clinical Observation and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 739 participants
- Where
- 914 sitesin 2 countries
- Study dates
- 3 Nov 2017to 1 Jan 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PRE-REGISTRATION ELIGIBILITY CRITERIA
- Histologically confirmed muscle-invasive urothelial carcinoma of the bladder, urethra, upper tract, or lymph node positive (LN+) disease; variant histology allowed as long as urothelial carcinoma is predominant (any amount of squamous differentiation is allowed); any component of neuroendocrine carcinoma is excluded
- Paraffin tissue samples obtained by transurethral resection of muscle-invasive bladder tumor, upper tract resection, or radical cystectomy/nephrectomy/ureterectomy/nephroureterectomy/cystoprostatectomy or urethrectomy must be available; this specimen submission is mandatory prior to registration as results will be used for stratification; specimens from radical/definitive surgery (radical cystectomy/nephrectomy/ureterectomy /nephroureterectomy/cystoprostatectomy and LN dissection) are preferred over transurethral resection, if available
- Patient must fit into one of the following three categories:
- Patients who received neoadjuvant chemotherapy and pathologic stage at surgical resection is >= pT2 and/or N+ OR
- Patients who are not cisplatin-eligible (according to >= 1 of the following criteria: Eastern Cooperative Oncology Group [ECOG] performance status of 2, creatinine clearance < 60 mL/min, grade >= 2 hearing loss, grade >= 2 neuropathy, or New York Heart Association class III heart failure and pathologic stage at surgical resection is >= pT3 or pN+) OR
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- Patients that decline adjuvant cisplatin-based or other systemic chemotherapy based on an informed discussion with the physician and pathologic stage at surgical resection is >= pT3 or pN+
- The 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized; patient must have had radical cystectomy (cystoprostatectomy for men) and lymph node dissection (for bladder primary), or nephrectomy, nephroureterectomy or ureterectomy (for uppertract tumors) or urethrectomy (in addition to a radical cystectomy-either simultaneously or in the past) >= 4 weeks but =< 16 weeks prior to pre-registration; patients who have had a partial cystectomy as definitive therapy are not eligible
- No gross cancer at the surgical margins; microscopic invasive urothelial carcinoma positive margins are allowed; carcinoma in situ (CIS) at margins is considered negative margins
- No evidence of residual cancer or metastasis after surgery; patients with upper tract urothelial carcinoma must have a negative cystoscopy within 3 months prior to pre-registration; if the bladder has been removed a cystoscopy is not required
- No metastatic disease (or radiologic findings "concerning" for metastatic disease) on cross-sectional imaging (according to Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1 criteria)
- No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease; human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible
- No current pneumonitis or prior history of non-infectious pneumonitis that required steroids within the previous 5 years
- Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
- Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
- No known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- No live vaccine within 30 days prior to the first dose of study drug; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
- No postoperative/adjuvant systemic therapy
- No prior treatment with any therapy on the PD-1/PD-L1 axis
- No treatment with any other type of investigational agent =< 4 weeks before pre-registration
- No major surgery =< 4 weeks before pre-registration
- No radiation therapy =< 4 weeks before pre-registration
- No neoadjuvant chemotherapy =< 4 weeks before pre-registration
- Not currently requiring hemodialysis
- Age >= 18 years
- Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
- ECOG performance status =< 2
- Absolute neutrophil count (ANC) >= 1,200/mm^3
- Leukocytes >= 3,000/ mm^3
- Platelet count >= 75,000/mm^3
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Bilirubin for patients with Gilbert's =< 3.0 x ULN
- Calculated (calc.) creatinine clearance >= 30 mL/min (using either Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation or Cockcroft-Gault formula)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit of normal (ULN)
- Serum albumin >= 2.8 g/dL
- For women of childbearing potential only: a negative urine or serum pregnancy test done =< 7 days prior to pre-registration is required
- REGISTRATION ELIGIBILITY CRITERIA: Results of central PD-L1 testing available; Q2 Solutions will forward the PD-L1 results to the statistical center and the statistical center will notify the site that the result is available; since the results with be blinded to the site the notification from the Alliance registration/randomization office will serve as a confirmation of this eligibility criteria; after sites receive the confirmation e-mail from Alliance they can register the patient
Who cannot join
None listed.
Trial locations and contacts
914 sites in 2 countries.
301 sites in 2 countries
United States300 sites
Hawaii Cancer Care - Westridge
‘Aiea, Hawaii, 96701
Pali Momi Medical Center
‘Aiea, Hawaii, 96701
Queen's Cancer Center - Pearlridge
‘Aiea, Hawaii, 96701
The Cancer Center of Hawaii-Pali Momi
‘Aiea, Hawaii, 96701
The Queen's Medical Center - West Oahu
‘Ewa Beach, Hawaii, 96706
Providence Regional Cancer System-Aberdeen
Aberdeen, Washington, 98520
Hendrick Medical Center
Abilene, Texas, 79601
Hickman Cancer Center
Adrian, Michigan, 49221
Summa Health System - Akron Campus
Akron, Ohio, 44304
Cleveland Clinic Akron General
Akron, Ohio, 44307
Christus Saint Frances Cabrini Hospital
Alexandria, Louisiana, 71301
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
OSF Saint Anthony's Health Center
Alton, Illinois, 62002
American Fork Hospital / Huntsman Intermountain Cancer Center
American Fork, Utah, 84003
Mary Greeley Medical Center
Ames, Iowa, 50010
McFarland Clinic - Ames
Ames, Iowa, 50010
Community Hospital of Anaconda
Anaconda, Montana, 59711
Kaiser Permanente-Anaheim
Anaheim, California, 92806
Anchorage Associates in Radiation Medicine
Anchorage, Alaska, 98508
Anchorage Radiation Therapy Center
Anchorage, Alaska, 99504
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, 99508
Alaska Oncology and Hematology LLC
Anchorage, Alaska, 99508
Alaska Women's Cancer Care
Anchorage, Alaska, 99508
Anchorage Oncology Centre
Anchorage, Alaska, 99508
Katmai Oncology Group
Anchorage, Alaska, 99508
Providence Alaska Medical Center
Anchorage, Alaska, 99508
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911
Mission Hope Medical Oncology - Arroyo Grande
Arroyo Grande, California, 93420
PCR Oncology
Arroyo Grande, California, 93420
Mission Hospital
Asheville, North Carolina, 28801
AdventHealth Infusion Center Asheville
Asheville, North Carolina, 28803
Messino Cancer Centers
Asheville, North Carolina, 28806
Grady Health System
Atlanta, Georgia, 30303
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342
Northside Hospital
Atlanta, Georgia, 30342
MultiCare Auburn Medical Center
Auburn, Washington, 98001
Harold Alfond Center for Cancer Care
Augusta, Maine, 04330
Rocky Mountain Cancer Centers-Aurora
Aurora, Colorado, 80012
The Medical Center of Aurora
Aurora, Colorado, 80012
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
Rush-Copley Medical Center
Aurora, Illinois, 60504
Mount Sinai Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180
Virginia Mason Bainbridge Island Medical Center
Bainbridge Island, Washington, 98110
Saint Alphonsus Cancer Care Center-Baker City
Baker City, Oregon, 97814
AIS Cancer Center at San Joaquin Community Hospital
Bakersfield, California, 93301
Kaiser Permanente-Baldwin Park
Baldwin Park, California, 91706
Mercy Oncology and Hematology - Clayton-Clarkson
Ballwin, Missouri, 63011
MedStar Union Memorial Hospital
Baltimore, Maryland, 21218
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore, Maryland, 21237
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Eastern Maine Medical Center
Bangor, Maine, 04401
CommonSpirit Saint Joseph Hospital - Bardstown
Bardstown, Kentucky, 40004
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
LSU Health Baton Rouge-North Clinic
Baton Rouge, Louisiana, 70805
Our Lady of the Lake Physician Group
Baton Rouge, Louisiana, 70808
Louisiana Hematology Oncology Associates LLC
Baton Rouge, Louisiana, 70809
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809
Ochsner Health Center-Summa
Baton Rouge, Louisiana, 70809
Medical Center of Baton Rouge
Baton Rouge, Louisiana, 70816
Ochsner High Grove
Baton Rouge, Louisiana, 70836
Bronson Battle Creek
Battle Creek, Michigan, 49017
Indu and Raj Soin Medical Center
Beavercreek, Ohio, 45431
MaineHealth Waldo Hospital
Belfast, Maine, 04915
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123
Overlake Medical Center
Bellevue, Washington, 98004
Kaiser Permanente-Bellflower
Bellflower, California, 90706
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, 98225
Strecker Cancer Center-Belpre
Belpre, Ohio, 45714
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601
Saint Charles Health System
Bend, Oregon, 97701
Central Vermont Medical Center/National Life Cancer Treatment
Berlin Corners, Vermont, 05602
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
MaineHealth Maine Medical Center - Biddeford
Biddeford, Maine, 04005
Billings Clinic Cancer Center
Billings, Montana, 59101
Saint Vincent Healthcare
Billings, Montana, 59101
Saint Vincent Frontier Cancer Center
Billings, Montana, 59102
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Saint Elizabeth Boardman Hospital
Boardman, Ohio, 44512
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Central Care Cancer Center - Bolivar
Bolivar, Missouri, 65613
Parkland Health Center-Bonne Terre
Bonne Terre, Missouri, 63628
McFarland Clinic - Boone
Boone, Iowa, 50036
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Boston Medical Center
Boston, Massachusetts, 02118
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Boulder Community Foothills Hospital
Boulder, Colorado, 80303
Rocky Mountain Cancer Centers-Boulder
Boulder, Colorado, 80304
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Cox Cancer Center Branson
Branson, Missouri, 65616
Lafayette Family Cancer Center-EMMC
Brewer, Maine, 04412
Ocean University Medical Center
Brick, New Jersey, 08724
United Hospital Center
Bridgeport, West Virginia, 26330
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
University of Michigan - Brighton Center for Specialty Care
Brighton, Michigan, 48116
Bristol Regional Medical Center
Bristol, Tennessee, 37620
Ballad Health Cancer Care - Bristol
Bristol, Virginia, 24201
Ascension Southeast Wisconsin Hospital-Elmbrook Campus-Brookfield
Brookfield, Wisconsin, 53045
Maimonides Medical Center
Brooklyn, New York, 11219
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183
Saint Joseph Regional Cancer Center
Bryan, Texas, 77802
Roswell Park Cancer Institute
Buffalo, New York, 14263
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, 91505
Saint Anne Hospital
Burien, Washington, 98166
Lahey Clinic
Burlington, Massachusetts, 01805
University of Vermont Medical Center
Burlington, Vermont, 05401
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
Aurora Cancer Care-Southern Lakes VLCC
Burlington, Wisconsin, 53105
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337
Loyola Center for Health at Burr Ridge
Burr Ridge, Illinois, 60527
Saint James Community Hospital and Cancer Treatment Center
Butte, Montana, 59701
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Cambridge Medical Center
Cambridge, Minnesota, 55008
Illinois CancerCare-Canton
Canton, Illinois, 61520
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health Medical Center - Canton
Canton, Michigan, 48188
Mercy Cancer Center - Cape Girardeau
Cape Girardeau, Missouri, 63703
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
AtlantiCare Health Park-Cape May Court House
Cape May Court House, New Jersey, 08210
Memorial Hospital of Carbondale
Carbondale, Illinois, 62902
Caro Cancer Center
Caro, Michigan, 48723
Saint Anthony Regional Hospital
Carroll, Iowa, 51401
Carson Tahoe Regional Medical Center
Carson City, Nevada, 89703
SIH Cancer Institute
Carterville, Illinois, 62918
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Duke Cancer Center Cary
Cary, North Carolina, 27518
Sandra L Maxwell Cancer Center
Cedar City, Utah, 84720
Rocky Mountain Cancer Centers - Centennial
Centennial, Colorado, 80112
Dayton Physicians LLC-Miami Valley South
Centerville, Ohio, 45459
Miami Valley Hospital South
Centerville, Ohio, 45459
Centralia Oncology Clinic
Centralia, Illinois, 62801
Providence Regional Cancer System-Centralia
Centralia, Washington, 98531
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Vandalia Health/CAMC Institute for Academic Medicine
Charleston, West Virginia, 25304
Chelsea Hospital
Chelsea, Michigan, 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Cheyenne Regional Medical Center-West
Cheyenne, Wyoming, 82001
Northwestern University
Chicago, Illinois, 60611
Rush MD Anderson Cancer Center
Chicago, Illinois, 60612
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Adena Regional Medical Center
Chillicothe, Ohio, 45601
Marshfield Clinic-Chippewa Center
Chippewa Falls, Wisconsin, 54729
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, 45220
Oncology Hematology Care Inc-Kenwood
Cincinnati, Ohio, 45236
Bethesda North Hospital
Cincinnati, Ohio, 45242
TriHealth Cancer Institute-Westside
Cincinnati, Ohio, 45247
TriHealth Cancer Institute-Anderson
Cincinnati, Ohio, 45255
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015
Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon, 97015
Hematology Oncology Consultants-Clarkston
Clarkston, Michigan, 48346
Newland Medical Associates-Clarkston
Clarkston, Michigan, 48346
MetroHealth Medical Center
Cleveland, Ohio, 44109
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina, 28328
Prisma Health Cancer Institute - Laurens
Clinton, South Carolina, 29325
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
AdventHealth Infusion Center Haywood
Clyde, North Carolina, 28721
Billings Clinic-Cody
Cody, Wyoming, 82414
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Coffeyville Regional Medical Center
Coffeyville, Kansas, 67337
Baptist Memorial Hospital and Cancer Center-Collierville
Collierville, Tennessee, 38017
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, 80907
Rocky Mountain Cancer Centers-Penrose
Colorado Springs, Colorado, 80907
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, 80909
Memorial Hospital North
Colorado Springs, Colorado, 80920
MU Health - University Hospital/Ellis Fischel Cancer Center
Columbia, Missouri, 65212
Baptist Memorial Hospital and Cancer Center-Golden Triangle
Columbus, Mississippi, 39705
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Mount Carmel East Hospital
Columbus, Ohio, 43213
Columbus Oncology and Hematology Associates Inc
Columbus, Ohio, 43214
Riverside Methodist Hospital
Columbus, Ohio, 43214
Grant Medical Center
Columbus, Ohio, 43215
The Mark H Zangmeister Center
Columbus, Ohio, 43219
Mount Carmel Health Center West
Columbus, Ohio, 43222
Doctors Hospital
Columbus, Ohio, 43228
Memorial Sloan Kettering Commack
Commack, New York, 11725
New Hampshire Oncology Hematology PA-Concord
Concord, New Hampshire, 03301
Mercy Hospital
Coon Rapids, Minnesota, 55433
Bay Area Hospital
Coos Bay, Oregon, 97420
Baptist Health Corbin
Corbin, Kentucky, 40701
Commonwealth Cancer Center-Corbin
Corbin, Kentucky, 40701
Good Samaritan Hospital
Corvallis, Oregon, 97330
Alegent Health Mercy Hospital
Council Bluffs, Iowa, 51503
Northshore Oncology Associates-Covington
Covington, Louisiana, 70433
Greater Regional Medical Center
Creston, Iowa, 50801
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Northside Hospital-Forsyth
Cumming, Georgia, 30041
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Danbury Hospital
Danbury, Connecticut, 06810
Carle at The Riverfront
Danville, Illinois, 61832
Geisinger Medical Center
Danville, Pennsylvania, 17822
MercyOne Genesis Davenport Medical Center
Davenport, Iowa, 52803
MercyOne Genesis Davenport Cancer Center
Davenport, Iowa, 52804
Iowa Cancer Specialists
Davenport, Iowa, 52807
Good Samaritan Hospital - Dayton
Dayton, Ohio, 45406
Miami Valley Hospital
Dayton, Ohio, 45409
Dayton Physician LLC - Englewood
Dayton, Ohio, 45415
Miami Valley Hospital North
Dayton, Ohio, 45415
Dayton Veterans Affairs Medical Center
Dayton, Ohio, 45428
Corewell Health Dearborn Hospital
Dearborn, Michigan, 48124
Henry Ford Medical Center-Fairlane
Dearborn, Michigan, 48126
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Delaware Health Center-Grady Cancer Center
Delaware, Ohio, 43015
Delaware Radiation Oncology
Delaware, Ohio, 43015
Grady Memorial Hospital
Delaware, Ohio, 43015
Cancer Center of Colorado at Sloan's Lake
Denver, Colorado, 80204
Kaiser Permanente-Franklin
Denver, Colorado, 80205
National Jewish Health-Main Campus
Denver, Colorado, 80206
The Women's Imaging Center
Denver, Colorado, 80209
AdventHealth Porter
Denver, Colorado, 80210
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, 80218
Rocky Mountain Cancer Centers-Midtown
Denver, Colorado, 80218
Saint Joseph Hospital - Cancer Centers of Colorado
Denver, Colorado, 80218
Rocky Mountain Cancer Centers-Rose
Denver, Colorado, 80220
Rose Medical Center
Denver, Colorado, 80220
Western Surgical Care
Denver, Colorado, 80220
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
Broadlawns Medical Center
Des Moines, Iowa, 50314
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
Iowa Lutheran Hospital
Des Moines, Iowa, 50316
Henry Ford Hospital
Detroit, Michigan, 48202
Henry Ford Health Saint John Hospital
Detroit, Michigan, 48236
Illinois CancerCare-Dixon
Dixon, Illinois, 61021
Doylestown Hospital
Doylestown, Pennsylvania, 18901
Epic Care-Dublin
Dublin, California, 94568
Dublin Methodist Hospital
Dublin, Ohio, 43016
Northside Hospital - Duluth
Duluth, Georgia, 30096
CommonSpirit Cancer Center Mercy
Durango, Colorado, 81301
Mercy Medical Center
Durango, Colorado, 81301
Duke University Medical Center
Durham, North Carolina, 27710
Prisma Health Cancer Institute - Easley
Easley, South Carolina, 29640
Henry Ford River District Hospital
East China Township, Michigan, 48054
Pocono Medical Center
East Stroudsburg, Pennsylvania, 18301
HSHS Sacred Heart Hospital
Eau Claire, Wisconsin, 54701
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
Mayo Clinic Health System-Eau Claire Clinic
Eau Claire, Wisconsin, 54701
Fairview Southdale Hospital
Edina, Minnesota, 55435
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
AtlantiCare Surgery Center
Egg Harbor, New Jersey, 08234
Bay Area Breast Surgeons Inc
Emeryville, California, 94608
Epic Care Partners in Cancer Care
Emeryville, California, 94608
Walter Knox Memorial Hospital
Emmett, Idaho, 83617
Mountain Blue Cancer Care Center - Swedish
Englewood, Colorado, 80113
Rocky Mountain Cancer Centers - Swedish
Englewood, Colorado, 80113
Swedish Medical Center
Englewood, Colorado, 80113
The Melanoma and Skin Cancer Institute
Englewood, Colorado, 80113
Saint Elizabeth Hospital
Enumclaw, Washington, 98022
OSF Saint Francis Hospital and Medical Group
Escanaba, Michigan, 49829
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201
Providence Regional Cancer Partnership
Everett, Washington, 98201
Fairbanks Memorial Hospital
Fairbanks, Alaska, 99701
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, 06824
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Sanford South University Medical Center
Fargo, North Dakota, 58103
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Parkland Health Center - Farmington
Farmington, Missouri, 63640
Virginia Mason Federal Way Medical Center
Federal Way, Washington, 98002
Saint Francis Hospital
Federal Way, Washington, 98003
Armes Family Cancer Center
Findlay, Ohio, 45840
Blanchard Valley Hospital
Findlay, Ohio, 45840
Orion Cancer Care
Findlay, Ohio, 45840
Augusta Health Center for Cancer and Blood Disorders
Fishersville, Virginia, 22939
Cancer Hematology Centers - Flint
Flint, Michigan, 48503
Genesee Hematology Oncology PC
Flint, Michigan, 48503
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
Aurora Health Center-Fond du Lac
Fond du Lac, Wisconsin, 54937
Kaiser Permanente-Fontana
Fontana, California, 92335
Poudre Valley Hospital
Fort Collins, Colorado, 80524
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501
UI Healthcare Mission Cancer and Blood - Fort Dodge
Fort Dodge, Iowa, 50501
Holy Cross Hospital
Fort Lauderdale, Florida, 33308
Mercy Hospital Fort Smith
Fort Smith, Arkansas, 72903
About this study
Official title: Phase III Randomized Adjuvant Study of Pembrolizumab in muScle invaSive and locAlly aDvanced urOthelial caRcinoma (AMBASSADOR) Versus Observation
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.
Read the detailed description
DUAL PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- 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:
- 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:
- 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.
- 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 10 years.
- Conditions
- Localized Renal Pelvis and Ureter Urothelial Carcinoma, Locally Advanced Bladder Urothelial Carcinoma, Locally Advanced Renal Pelvis and Ureter Urothelial Carcinoma, Locally Advanced Ureter Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma AJCC v6 and v7
- Being tested
- Biospecimen Collection, Clinical Observation, Computed Tomography, CT Urography, Cystoscopy
- Medical subject headings
- Ureteral Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Clinical ObservationOther
Also called observation
Undergo observation
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo a CT scan
CT UrographyProcedure or surgery
Also called Urography Computed Tomography
Undergo a CT urography
CystoscopyProcedure or surgery
Also called CS
Undergo a cystoscopy
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo a MRI
PembrolizumabBiological
Also called BCD-201, GME 751, GME751, Keytruda
Given IV
Correlative studies
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm A (pembrolizumab) | Experimental | Patients receive pembrolizumab 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 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: CT Urography; Procedure: Cystoscopy; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Arm B (observation) | Active comparator | 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. Receives: Procedure: Biospecimen Collection; Other: Clinical Observation; Procedure: Computed Tomography; Procedure: CT Urography; Procedure: Cystoscopy; Procedure: Magnetic Resonance Imaging; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
Measured: From randomization to the date of death from any cause, assessed up to 5 years
Disease-free survival
The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
Measured: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years
Secondary outcomes (2)
Overall survival in PD-L1 positive and negative patients
The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
Measured: From randomization to the date of death from any cause, assessed up to 5 years
Disease-free survival in PD-L1 positive and negative patients
The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
Measured: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2017
- Study start3 Nov 2017
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Localized Renal Pelvis and Ureter Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 739 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Andrea B Apolo, Principal investigator, Alliance for Clinical Trials in Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03244384
- Sponsor's protocol ID
- NCI-2017-01425
- Other IDs
- NCI-2017-01425, A031501, A031501, A031501, U10CA180821
- Acronym
- AMBASSADOR
- Status last verified
- Oct 2026
- First submitted
- 7 Aug 2017
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Apolo AB, Ballman KV, Sonpavde G, Berg S, Kim WY, Parikh R, Teo MY, Sweis RF, Geynisman DM, Grivas P, Chatta G, Reichert ZR, Kim JW, Bilen MA, McGregor B, Singh P, Tripathi A, Cole S, Simon N, Niglio S, Ley L, Cordes L, Srinivas S, Huang J, Odegaard M, Watt C, Petrylak D, Hoffman-Censits J, Wen Y, Hahn O, Mitchell C, Tan A, Streicher H, Sharon E, Moon H, Woods M, Halabi S, Perez Burbano G, Morris MJ, Rosenberg JE. Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2025 Jan 2;392(1):45-55. doi: 10.1056/NEJMoa2401726. Epub 2024 Sep 15.
PubMed 39282902