Atezolizumab in Treating Patients With Recurrent BCG-Unresponsive Non-muscle Invasive Bladder Cancer

Phase II Trial of Atezolizumab in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer

This phase II trial studies how well atezolizumab works in treating patients with non-muscle invasive bladder cancer that has come back (recurrent) and has not responded to treatment (refractory) with Bacillus Calmette-Guerin (BCG). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrent Bladder Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma AJCC v6 and v7; Stage 0is Bladder Urothelial Carcinoma AJCC v6 and v7; Stage I Bladder Urothelial Carcinoma AJCC v6 and v7
• Intervention / Treatment: Drug: Atezolizumab

Detailed Description

PRIMARY OBJECTIVE:

I. To estimate complete response at 25 weeks after registration for those with a carcinoma in situ (CIS) component and to evaluate event-free survival at 18 months in patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer (Ta/T1/CIS) treated with atezolizumab.

SECONDARY OBJECTIVES:

I. To estimate event-free survival at 18 months for the subset of patients with papillary cancer (Ta/T1).

II. To estimate progression-free survival, cystectomy-free survival, bladder cancer-specific survival, overall survival in all patients.

ADDITIONAL OBJECTIVES:

I. To estimate the level of agreement between local and central pathology review in terms of recurrence (for all patients) and complete response (for the CIS subset).

II. To identify markers that predict response to atezolizumab in the CIS population and that are associated with event-free survival (EFS) in patients with Ta/T1/CIS BCG-unresponsive non-muscle invasive bladder cancer. The following markers will be tested:

IIIa. Expression of PD-L1 and CD8 by immunohistochemistry (IHC). IIIb. Expression of immune signatures by ribonucleic acid (RNA)-sequencing (RNA-seq).

IIIc. Peripheral immune response by mass cytometry (CyTOF) and TruCulture.

OUTLINE:

Patients receive atezolizumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles (51 weeks) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 2 years and then every 24 weeks for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 172
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Quebec
    • Montreal, Quebec, Canada, H3H 2R9
      • The Research Institute of the McGill University Health Centre (MUHC)
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
• United States
  • Alabama
    • Daphne, Alabama, United States, 36526
      • Southern Cancer Center PC-Daphne
    • Mobile, Alabama, United States, 36607
      • Southern Cancer Center PC-Mobile
    • Mobile, Alabama, United States, 36608
      • Southern Cancer Center PC-Providence
    • Mobile, Alabama, United States, 36608
      • Southern Cancer Center PC-Springhill
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
    • Tucson, Arizona, United States, 85704
      • University of Arizona Cancer Center-Orange Grove Campus
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center-North Campus
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • John L McClellan Memorial Veterans Hospital
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles General Medical Center
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Rancho Mirage, California, United States, 92270
      • Eisenhower Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • San Francisco, California, United States, 94158
      • UCSF Medical Center-Mission Bay
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UCHealth University of Colorado Hospital
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente-Franklin
    • Lafayette, Colorado, United States, 80026
      • Kaiser Permanente-Rock Creek
    • Lone Tree, Colorado, United States, 80124
      • Kaiser Permanente-Lone Tree
  • Connecticut
    • Greenwich, Connecticut, United States, 06830
      • Greenwich Hospital
    • New Haven, Connecticut, United States, 06520
      • Yale University
    • West Haven, Connecticut, United States, 06516
      • Veterans Affairs Connecticut Healthcare System-West Haven Campus
  • Delaware
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Delaware Clinical and Laboratory Physicians PA
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Wilmington, Delaware, United States, 19801
      • Christiana Care Health System-Wilmington Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
    • Washington, District of Columbia, United States, 20037
      • George Washington University Medical Center
  • Florida
    • Aventura, Florida, United States, 33180
      • Mount Sinai Comprehensive Cancer Center at Aventura
    • Gainesville, Florida, United States, 32610
      • University of Florida Health Science Center - Gainesville
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Vero Beach, Florida, United States, 32960
      • Indian River Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Decatur, Georgia, United States, 30033
      • Atlanta VA Medical Center
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc - Waterfront Plaza
    • Honolulu, Hawaii, United States, 96813
      • Queen's Cancer Cenrer - POB I
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96817
      • Queen's Cancer Center - Kuakini
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96813
      • Island Urology
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
    • Caldwell, Idaho, United States, 83605
      • Saint Alphonsus Cancer Care Center-Caldwell
    • Emmett, Idaho, United States, 83617
      • Walter Knox Memorial Hospital
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute-Meridian
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Cancer Institute - Meridian
    • Nampa, Idaho, United States, 83687
      • Saint Alphonsus Cancer Care Center-Nampa
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Cancer Institute - Twin Falls
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Elmhurst, Illinois, United States, 60126
      • Elmhurst Memorial Hospital
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Hines, Illinois, United States, 60141
      • Edward Hines Jr VA Hospital
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Naperville, Illinois, United States, 60540
      • Edward Hospital/Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Plainfield, Illinois, United States, 60585
      • Edward Hospital/Cancer Center?Plainfield
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • The Carle Foundation Hospital
    • Yorkville, Illinois, United States, 60560
      • Rush-Copley Healthcare Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46219
      • Community Cancer Center East
    • Indianapolis, Indiana, United States, 46227
      • Community Cancer Center South
    • Indianapolis, Indiana, United States, 46256
      • Community Cancer Center North
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • Richmond, Indiana, United States, 47374
      • Reid Health
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Hays, Kansas, United States, 67601
      • HaysMed University of Kansas Health System
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67905
      • Cancer Center of Kansas-Liberal
    • Manhattan, Kansas, United States, 66502
      • Cancer Center of Kansas-Manhattan
    • McPherson, Kansas, United States, 67460
      • Cancer Center of Kansas - McPherson
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Olathe, Kansas, United States, 66061
      • Olathe Health Cancer Center
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pittsburg, Kansas, United States, 66762
      • Ascension Via Christi - Pittsburg
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Salina Regional Health Center
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Topeka, Kansas, United States, 66606
      • University of Kansas Health System Saint Francis Campus
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Westwood, Kansas, United States, 66205
      • University of Kansas Hospital-Westwood Cancer Center
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • East Jefferson General Hospital
    • Metairie, Louisiana, United States, 70006
      • LSU Healthcare Network / Metairie Multi-Specialty Clinic
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Science Center
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Sciences Center at Shreveport
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Lowell, Massachusetts, United States, 01854
      • Lowell General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Brighton, Michigan, United States, 48114
      • Saint Joseph Mercy Brighton
    • Brighton, Michigan, United States, 48114
      • Trinity Health IHA Medical Group Hematology Oncology - Brighton
    • Canton, Michigan, United States, 48188
      • Saint Joseph Mercy Canton
    • Canton, Michigan, United States, 48188
      • Trinity Health IHA Medical Group Hematology Oncology - Canton
    • Caro, Michigan, United States, 48723
      • Caro Cancer Center
    • Chelsea, Michigan, United States, 48118
      • Saint Joseph Mercy Chelsea
    • Chelsea, Michigan, United States, 48118
      • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
    • Clarkston, Michigan, United States, 48346
      • Hematology Oncology Consultants-Clarkston
    • Clarkston, Michigan, United States, 48346
      • Newland Medical Associates-Clarkston
    • East Lansing, Michigan, United States, 48824
      • Michigan State University Clinical Center
    • Flint, Michigan, United States, 48503
      • Genesee Cancer and Blood Disease Treatment Center
    • Flint, Michigan, United States, 48503
      • Genesee Hematology Oncology PC
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Lansing, Michigan, United States, 48912
      • University of Michigan Health - Sparrow Lansing
    • Marlette, Michigan, United States, 48453
      • Saint Mary's Oncology/Hematology Associates of Marlette
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Pontiac, Michigan, United States, 48341
      • Newland Medical Associates-Pontiac
    • Saginaw, Michigan, United States, 48601
      • Ascension Saint Mary's Hospital
    • Saginaw, Michigan, United States, 48604
      • Oncology Hematology Associates of Saginaw Valley PC
    • West Branch, Michigan, United States, 48661
      • Saint Mary's Oncology/Hematology Associates of West Branch
    • Ypsilanti, Michigan, United States, 48197
      • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
    • Ypsilanti, Michigan, United States, 48106
      • Huron Gastroenterology PC
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Deer River, Minnesota, United States, 56636
      • Essentia Health - Deer River Clinic
    • Duluth, Minnesota, United States, 55805
      • Saint Luke's Hospital of Duluth
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Saint Mary's Medical Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Hibbing, Minnesota, United States, 55746
      • Essentia Health Hibbing Clinic
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center at Saint Cloud Hospital
    • Saint Cloud, Minnesota, United States, 56303
      • Saint Cloud Hospital
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Virginia, Minnesota, United States, 55792
      • Essentia Health Virginia Clinic
    • Wyoming, Minnesota, United States, 55092
      • Fairview Lakes Medical Center
  • Missouri
    • Bonne Terre, Missouri, United States, 63628
      • Parkland Health Center-Bonne Terre
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Columbia, Missouri, United States, 65212
      • MU Health - University Hospital/Ellis Fischel Cancer Center
    • Kansas City, Missouri, United States, 64128
      • Kansas City Veterans Affairs Medical Center
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • BJC Outpatient Center at Sunset Hills
  • Montana
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68118
      • Nebraska Medicine-Village Pointe
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Cancer and Blood Specialists-Henderson
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada - Northwest
    • Las Vegas, Nevada, United States, 89128
      • OptumCare Cancer Care at MountainView
    • Las Vegas, Nevada, United States, 89144
      • Comprehensive Cancer Centers of Nevada - Town Center
    • Las Vegas, Nevada, United States, 89148
      • Comprehensive Cancer Centers of Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada - Central Valley
    • Las Vegas, Nevada, United States, 89128
      • Ann M Wierman MD LTD
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
  • New Jersey
    • Somerville, New Jersey, United States, 08876
      • Robert Wood Johnson University Hospital Somerset
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10019
      • Mount Sinai West
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center-Clinton
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center-Jacksonville
    • Salisbury, North Carolina, United States, 28144
      • WG Hefner VA Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Roger Maris Cancer Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Broadway Medical Center
  • Ohio
    • Dayton, Ohio, United States, 45415
      • Dayton Physician LLC-Miami Valley Hospital North
    • Dayton, Ohio, United States, 45415
      • Miami Valley Hospital North
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lima, Ohio, United States, 45801
      • Saint Rita's Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Hospital Oklahoma City
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute-Tulsa
  • Oregon
    • Baker City, Oregon, United States, 97814
      • Saint Alphonsus Medical Center-Baker City
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Ontario, Oregon, United States, 97914
      • Saint Alphonsus Medical Center-Ontario
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • Pennsylvania
    • Chadds Ford, Pennsylvania, United States, 19317
      • Christiana Care Health System-Concord Health Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • South Carolina
    • Boiling Springs, South Carolina, United States, 29316
      • Prisma Health Cancer Institute - Spartanburg
    • Clinton, South Carolina, United States, 29325
      • Prisma Health Cancer Institute - Laurens
    • Easley, South Carolina, United States, 29640
      • Prisma Health Cancer Institute - Easley
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Butternut
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Greenville Memorial Hospital
    • Greer, South Carolina, United States, 29650
      • Prisma Health Cancer Institute - Greer
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic
  • Texas
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
    • League City, Texas, United States, 77573
      • UTMB Cancer Center at Victory Lakes
    • San Antonio, Texas, United States, 78229
      • University Hospital
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • Audie L Murphy VA Hospital
  • Utah
    • Farmington, Utah, United States, 84025
      • Farmington Health Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • South Jordan, Utah, United States, 84009
      • South Jordan Health Center
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Centra Lynchburg Hematology-Oncology Clinic Inc
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-First Hill
    • Vancouver, Washington, United States, 98686
      • Legacy Salmon Creek Hospital
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston Division
  • Wisconsin
    • Ashland, Wisconsin, United States, 54806
      • Duluth Clinic Ashland
    • Burlington, Wisconsin, United States, 53105
      • Aurora Cancer Care-Southern Lakes VLCC
    • Chippewa Falls, Wisconsin, United States, 54729
      • Marshfield Clinic-Chippewa Center
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Medical Center-EC Cancer Center
    • Fond Du Lac, Wisconsin, United States, 54937
      • Aurora Health Center-Fond du Lac
    • Germantown, Wisconsin, United States, 53022
      • Aurora Health Care Germantown Health Center
    • Grafton, Wisconsin, United States, 53024
      • Aurora Cancer Care-Grafton
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • Ladysmith, Wisconsin, United States, 54848
      • Marshfield Clinic - Ladysmith Center
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center
    • Marinette, Wisconsin, United States, 54143
      • Aurora Bay Area Medical Group-Marinette
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield
    • Milwaukee, Wisconsin, United States, 53209
      • Aurora Cancer Care-Milwaukee
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic-Minocqua Center
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Racine, Wisconsin, United States, 53406
      • Aurora Cancer Care-Racine
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Medical Center-Rice Lake
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • Stevens Point, Wisconsin, United States, 54482
      • Marshfield Medical Center-River Region at Stevens Point
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • Wausau, Wisconsin, United States, 54401
      • Marshfield Clinic-Wausau Center
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center
    • Weston, Wisconsin, United States, 54476
      • Marshfield Medical Center - Weston
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have histologically proven, recurrent, non-muscle invasive urothelial carcinoma of the bladder within 60 days prior to registration; the carcinoma must be stage T1 high-grade, stage CIS, or stage Ta high-grade
• Patients with mixed urothelial carcinoma and a glandular and/or squamous component will be eligible for the trial, but the presence of other histologic variants, pure adenocarcinoma, or pure squamous cell carcinoma, or pure squamous carcinoma in situ will make a patient ineligible
• Patients must have had all visible tumor resected completely within 60 days prior to registration; CIS disease is not expected to be completely excised; all patients must have tumor tissue from the histologic diagnosis of recurrence available for central pathology review submission; failure to submit these materials will make the patient ineligible for this study
• Patients must have had cystoscopy confirming no visible papillary tumor within 21 days prior to registration; (CIS disease is not expected to have been completely excised); if the transurethral resection of bladder tumor (TURBT) or bladder biopsy falls within 21 days of registration it will fulfill this criterion
• Patients must have had urine cytology within 21 days prior to registration; cytology for patients with CIS component is not expected to be negative for malignant cells; if the cytology for male patients with only Ta/T1 disease in the absence of CIS is positive for malignant cells, patient must have had a biopsy of the prostatic urethra within the previous six months
• All patients with T1 urothelial carcinoma at study entry must undergo re-TURBT within 60 days prior to registration, and must have evidence of uninvolved muscularis propria in the pathologic specimen from either the first or the second TURBT; tissue from the re-resection must be submitted for central review in addition to the tissue from the first TURBT; the TURBT that identified the recurrent T1 disease may have taken place more than 60 days prior to registration but not more than 120 days; patients with high grade Ta or CIS do not require a re-TURBT, but if this is performed at the discretion of the treating physician, the second TURBT must be within 60 days of registration; there is no requirement for muscularis propria in the specimen of Ta/CIS patients, but the tissue from the first and second TURBTs must be submitted for central review; if a patient with Ta/T1 disease undergoes repeat TURBT, the patient will be stratified as having CIS if there is CIS on either TURBT
• Patients must not have had urothelial carcinoma in the prostatic urethra within the previous 24 months or muscle invasive urothelial carcinoma of the bladder at any time; patients with prior urothelial carcinoma in the upper urinary tract within the previous 24 months will only be eligible if they had =< T1 carcinoma and were treated with nephroureterectomy; patients must have a computed tomography (CT) or magnetic resonance imaging (MRI) (including CT-intravenous pyelogram [IVP], CT-urogram or MR-urogram) of the abdomen and pelvis to rule out upper tract malignancy and intra-abdominal metastases within 90 days prior to registration; if a patient cannot tolerate intravenous contrast, a retrograde pyelogram should be performed within 90 days prior to registration
• Patients must be deemed unfit for radical cystectomy by the treating physician, or the patient must refuse radical cystectomy, which is considered standard of care for these patients; the reason for patients not to undergo cystectomy will be clearly documented

• Patients must be BCG-unresponsive; a patient is BCG-unresponsive if they meet one or more of the following criteria:

  • Patient has persistent or recurrent high-grade Ta/CIS urothelial carcinoma after completing therapy with at least induction BCG (>= 5 doses) and first round maintenance (>= 2 doses) or second induction BCG (>= 2 doses); both rounds of BCG must have been administered within a 12 month period; these patients must have either had high-grade Ta tumors and did not achieve a disease-free state for more than 6 months following last dose of BCG, or they had CIS and did not achieve a CR; S1605 registration must occur within 9 months of the last dose of BCG

    • If a patient does not meet these criteria only because the last dose of BCG was more than 9 months ago, the patient may become eligible if he/she shows histologically proven high-grade recurrence after an additional round of induction or maintenance BCG (>= 3 doses) within 9 months prior to registration

  • Patient has persistent or recurrent high grade T1 urothelial carcinoma after completing therapy with at least induction BCG (>= 5 doses); patients with recurrent high grade T1 urothelial carcinoma after additional rounds of BCG will also be eligible, but one round of maintenance therapy or a second induction is not a pre-requisite for these patients. Trial registration must occur within 9 months of the last dose of BCG

    • If a patient does not meet these criteria only because the last dose of BCG was more than 9 months ago, the patient may become eligible if he/she shows histologically proven high grade recurrence after an additional round of induction or maintenance BCG (>= 3 doses) within 9 months prior to registration
  • Patient achieves disease-free state at 6 month time point (i.e., complete response; presence of only low-grade tumor at this timepoint is still considered complete response) after induction and maintenance (or second round of induction) BCG but later experiences a high-grade Ta/T1 recurrence (with or without concomitant CIS) within 6 months after the last dose of BCG or recurrent CIS (in absence of concomitant Ta/T1 tumor) within 12 months after the last BCG dose; the time of eligibility is measured from the last dose of BCG to the time of disease recurrence; the patient must be registered on the trial within 60 days of this recurrence, or within 60 days of a re-TURBT if indicated
• All adverse events associated with any prior surgery and intravesical therapy must have resolved to grade =< 2 prior to registration
• Absolute neutrophil count (ANC) >= 1,500 microliter (mcL) (within 42 days prior to registration)
• Platelets >= 100,000/mcL (within 42 days prior to registration)
• Hemoglobin >= 9 g/dL (within 42 days prior to registration)
• Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 42 days prior to registration)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2 x IULN (within 42 days prior to registration)
• Serum creatinine =< 1.5 ULN OR measured or calculated creatinine clearance >= 30 mL/min (within 42 days prior to registration)
• Patients must have Zubrod performance status =< 2
• Patients must have a baseline electrocardiograph (ECG) performed within 42 days prior to registration

• Patients positive for human immunodeficiency virus (HIV) are eligible only if they have all of the following:

  • A stable regimen of highly active anti-retroviral therapy (HAART)
  • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
  • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests
• No other prior malignancy is allowed except, for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
• Patients must be offered the opportunity to participate in specimen banking for future studies, to include translational medicine studies
• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• As a part of the oncology patient enrollment network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Exclusion Criteria:

• Patients must not have had prior systemic chemotherapy for bladder cancer or systemic immunotherapy, including, but not limited to interferon alfa-2b, high dose interleukin 2 (IL-2), pegylated interferon (PEG-IFN), PD-1, anti-PD-L1, intra-tumoral; patients must not have had vaccine therapies within 6 weeks prior to registration; patients must not have received or be planning to receive any of the prohibited therapies during protocol treatment; prior intravesical administration of chemotherapy, interferon, Vicinium (VB4-485), BC-819 or Instiladrin (rAd-interferon-alpha/Syn3) is allowed if all other criteria are met and the last administration was >= 30 days before registration
• Patients must not be planning to receive concomitant other biologic therapy, radiation therapy, intravesical chemotherapy, surgery, or other anti-cancer therapy while on this protocol
• Patients must not have received any prior radiation to the bladder for bladder cancer
• Patients must not have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 4 weeks prior to registration; exceptions: (1) patients may have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea); (2) the use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed

• Patients must not have received a live, attenuated vaccine within 4 weeks before registration or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab

  • Influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine within 4 weeks prior to cycle 1, day 1 or at any time during the study
• Patients must not require treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumab
• Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis
• Patients must not have an active infection requiring oral or IV antibiotics within 14 days prior to registration; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
• Patients must not have severe infections within 28 days prior to registration, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Patients must not have active autoimmune disease that has required systemic treatment in past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; autoimmune diseases include, but are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
• Patients must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation
• Patient must not have active tuberculosis

• Patients must not have active hepatitis B (chronic or acute) or active hepatitis C infection

  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
• Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment; administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Due to the potential drug reaction with atezolizumab, patients must not be known to be allergic to Chinese hamster egg or ovaries

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (atezolizumab); Patients receive atezolizumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles (51 weeks) in the absence of disease progression or unacceptable toxicity.	Drug: Atezolizumab; Given IV; Other Names: Tecentriq; MPDL3280A; RO5541267; RG7446; MPDL 3280A; MPDL 328OA; MPDL-3280A; MPDL328OA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate in the Subset of Patients With Carcinoma in Situ (CIS)	To estimate complete response at 25 weeks after registration for those with a CIS component. Complete Response (CR) is defined as negative biopsy for high grade disease at Week 25 (± 7 days) for the subset of patients with a CIS component at study entry, according to local pathology call. In addition, patients with a CIS component who undergo negative biopsy at Week 13 for suspicious cystoscopy and or positive cytology and have cystoscopy not suspicious for cancer and cytology not positive for malignant cells at Week 25 do not require repeat biopsy at Week 25 and will be considered to have a complete response at Week 13 and will also be counted as having a complete response at Week 25.	At 25 weeks
Event-free Survival (EFS)	To evaluate event-free survival at 18 months in patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer (Ta/T1/CIS) treated with atezolizumab. Event-Free Survival is defined as time from date of registration to first documentation of event. Participants last known to be alive and not to have recurred are censored at the date of last contact. An event was defined as the first occurrence of any of the following: biopsy-proven high-grade bladder cancer (including persistent CIS at 3 and/or 6 months); high-grade upper tract urothelial carcinoma; high-grade urothelial carcinoma of the prostatic urethra; muscle-invasive disease; clinical evidence of metastatic disease; or death due to any cause.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free Survival (EFS) in the Ta/T1 Subset	To evaluate event-free survival at 18 months in the subset of participants with papillary cancer (Ta/T1) treated with atezolizumab. Event-Free Survival is defined as time from date of registration to first documentation of event. Participants last known to be alive and not to have recurred are censored at the date of last contact. An event was defined as the first occurrence of any of the following: biopsy-proven high-grade bladder cancer (including persistent CIS at 3 and/or 6 months); high-grade upper tract urothelial carcinoma; high-grade urothelial carcinoma of the prostatic urethra; muscle-invasive disease; clinical evidence of metastatic disease; or death due to any cause.	18 months
Progression-free Survival (PFS)	Progression-free survival (PFS) is defined as the time from registration to first evidence of biopsy-proven muscle-invasive bladder cancer (T>=2), nodal or distant metastasis, or death from any cause. Participants without an event were censored at the date of their last cystoscopy. Estimated using Kaplan-Meier.	From time of registration to time of first documentation progression or death due to any cause, assessed up to 5 years
Time to Cystectomy	Time to cystectomy is defined as time from discontinuation of protocol therapy to time of cystectomy.	Up to 5 years
Bladder Cancer-Specific Survival	Bladder cancer-specific survival is defined as the time from the date of registration to the date of death due to bladder cancer. Participants without bladder cancer death are censored at last contact date or date of non-bladder cancer death. Estimated using Kaplan-Meier.	From date of registration to date of death due to bladder cancer, assessed up to 5 years
Three-Year Overall Survival	Overall survival (OS) is defined as the time from registration to the date of death due to any cause. Participants last known to be alive are censored at the date of last contact.	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence in all patients	Will estimate the level of agreement between local and central pathology review.	Up to 5 years
CR for the CIS subset	Will estimate the level of agreement between local and central pathology review.	Up to 5 years
PD-L1 and CD8 expression	Logistic regression will be used to regress the dichotomous CR status of each CIS patient on the indicator of programmed cell death - ligand (PD-L)1 expression. Fisher's exact test may be used if the proportion of complete responders or proportion of patients expressing PD-L1 is small. Similarly, using all patients, logistic regression will also be used to regress dichotomous 18-month EFS status of each patient on the indicator PD-L1 expression. The analysis will be repeated with CD8 expression as well as other markers. The type I error rate will be controlled at the two-sided alpha=0.05.	Up to 5 years
Immune signature expression	Logistic regression will be used to regress CR status for each CIS patient on an indicator for whether each patient expresses the signature. Similarly, to determine whether pre-defined signatures are predictive of 18-month EFS in all patients, logistic regression will be used to regress 18-month EFS status for each patient on an indicator for whether each patient expresses the signature. This analysis will be repeated for each signature considered. Investigators will again consider using Fisher's exact test if the CR or 18-month EFS rates or the proportion of patients expressing the signature are low. Type I error rate will be controlled at the 2-sided alpha=0.05 level.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Canadian Cancer Trials Group
• Investigators: Principal Investigator: Peter C Black, SWOG Cancer Research Network

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2017
• Primary Completion (Actual): June 1, 2023
• Study Completion (Estimated): September 21, 2024

Study Registration Dates

• First Submitted: July 22, 2016
• First Submitted That Met QC Criteria: July 22, 2016
• First Posted (Estimated): July 26, 2016

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Carcinoma; Carcinoma, Transitional Cell; Non-Muscle Invasive Bladder Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antibodies, Monoclonal; Atezolizumab
• Other Study ID Numbers: NCI-2016-01104 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180888 (U.S. NIH Grant/Contract); S1605 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No