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

Recurrent Bladder Urothelial Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02844816
• Other study ID #: NCI-2016-01104
• Secondary ID: NCI-2016-01104S1
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 13, 2017
• Est. completion date: September 21, 2024

Study information

• Verified date: June 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 172
• Est. completion date: September 21, 2024
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• 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

Drug:
• Atezolizumab
Given IV

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	The Research Institute of the McGill University Health Centre (MUHC)	Montreal	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Saint Alphonsus Cancer Care Center-Baker City	Baker City	Oregon
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	Boston Medical Center	Boston	Massachusetts
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Trinity Health Medical Center - Brighton	Brighton	Michigan
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Trinity Health Medical Center - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Caro Cancer Center	Caro	Michigan
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Chelsea Hospital	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Prisma Health Cancer Institute - Laurens	Clinton	South Carolina
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	MU Health - University Hospital/Ellis Fischel Cancer Center	Columbia	Missouri
United States	Carle at The Riverfront	Danville	Illinois
United States	Southern Cancer Center PC-Daphne	Daphne	Alabama
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Kaiser Permanente-Franklin	Denver	Colorado
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Michigan State University Clinical Center	East Lansing	Michigan
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Farmington Health Center	Farmington	Utah
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	University of Texas Medical Branch	Galveston	Texas
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Greenwich Hospital	Greenwich	Connecticut
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	HaysMed	Hays	Kansas
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	Edward Hines Jr VA Hospital	Hines	Illinois
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Island Urology	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Community Cancer Center East	Indianapolis	Indiana
United States	Community Cancer Center North	Indianapolis	Indiana
United States	Community Cancer Center South	Indianapolis	Indiana
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Community Howard Regional Health	Kokomo	Indiana
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Marshfield Medical Center - Ladysmith	Ladysmith	Wisconsin
United States	Kaiser Permanente-Rock Creek	Lafayette	Colorado
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	UTMB Cancer Center at Victory Lakes	League City	Texas
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Saint Rita's Medical Center	Lima	Ohio
United States	John L McClellan Memorial Veterans Hospital	Little Rock	Arkansas
United States	Kaiser Permanente-Lone Tree	Lone Tree	Colorado
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Centra Alan B Pearson Regional Cancer Center	Lynchburg	Virginia
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	University of Wisconsin Carbone Cancer Center - University Hospital	Madison	Wisconsin
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Loyola University Medical Center	Maywood	Illinois
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	LSU Healthcare Network / Metairie Multi-Specialty Clinic	Metairie	Louisiana
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Southern Cancer Center PC-Mobile	Mobile	Alabama
United States	Southern Cancer Center PC-Providence	Mobile	Alabama
United States	Southern Cancer Center PC-Springhill	Mobile	Alabama
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	Yale University	New Haven	Connecticut
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	Mount Sinai West	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Alphonsus Cancer Care Center-Ontario	Ontario	Oregon
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Eisenhower Medical Center	Rancho Mirage	California
United States	Renown Regional Medical Center	Reno	Nevada
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Reid Health	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	University of Rochester	Rochester	New York
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salina Regional Health Center	Salina	Kansas
United States	WG Hefner VA Medical Center	Salisbury	North Carolina
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Audie L Murphy VA Hospital	San Antonio	Texas
United States	University Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	South Jordan Health Center	South Jordan	Utah
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	Indian River Medical Center	Vero Beach	Florida
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	George Washington University Medical Center	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	Veterans Affairs Connecticut Healthcare System-West Haven Campus	West Haven	Connecticut
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Canadian Cancer Trials Group

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	Time to Cystectomy	Time to cystectomy is defined as time from discontinuation of protocol therapy to time of cystectomy.	Up to 5 years
Secondary	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
Secondary	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