Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

172

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Mar 2017

Longer than P75 for phase_2

Geographic Reach

2 countries

272 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7.3 years study duration

First Submitted

Initial submission to the registry

July 22, 2016

Completed

4 days until next milestone

First Posted

Study publicly available on registry

July 26, 2016

Completed

8 months until next milestone

Study Start

First participant enrolled

March 13, 2017

Completed

6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2023

Completed

7 months until next milestone

Results Posted

Study results publicly available

December 15, 2023

Completed

6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 26, 2024

Completed

Last Updated

May 22, 2025

Status Verified

May 1, 2025

Enrollment Period

6.2 years

First QC Date

July 22, 2016

Results QC Date

October 17, 2023

Last Update Submit

May 12, 2025

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

Outcome Measures

Primary Outcomes (2)

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 Outcomes (5)

Event-free Survival (EFS) in the Ta/T1 Subset
18 months
Progression-free Survival (PFS)
18 months
Time to Cystectomy
Up to 5 years
Bladder Cancer-Specific Survival
3 years
Three-Year Overall Survival
3 years

Study Arms (1)

Treatment (atezolizumab)

EXPERIMENTAL

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

Interventions

AtezolizumabDRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Treatment (atezolizumab)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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
+16 more criteria

You may not qualify if:

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
+3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead
Canadian Cancer Trials Groupcollaborator

Study Sites (272)

Southern Cancer Center PC-Daphne

Daphne, Alabama, 36526, United States

Location

Southern Cancer Center PC-Mobile

Mobile, Alabama, 36607, United States

Location

Southern Cancer Center PC-Providence

Mobile, Alabama, 36608, United States

Location

Southern Cancer Center PC-Springhill

Mobile, Alabama, 36608, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Arizona Cancer Center-Orange Grove Campus

Tucson, Arizona, 85704, United States

Location

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

Location

University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719, United States

Location

John L McClellan Memorial Veterans Hospital

Little Rock, Arkansas, 72205, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

Eisenhower Medical Center

Rancho Mirage, California, 92270, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Kaiser Permanente-Franklin

Denver, Colorado, 80205, United States

Location

Kaiser Permanente-Rock Creek

Lafayette, Colorado, 80026, United States

Location

Kaiser Permanente-Lone Tree

Lone Tree, Colorado, 80124, United States

Location

Greenwich Hospital

Greenwich, Connecticut, 06830, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Veterans Affairs Connecticut Healthcare System-West Haven Campus

West Haven, Connecticut, 06516, United States

Location

Delaware Clinical and Laboratory Physicians PA

Newark, Delaware, 19713, United States

Location

Helen F Graham Cancer Center

Newark, Delaware, 19713, United States

Location

Medical Oncology Hematology Consultants PA

Newark, Delaware, 19713, United States

Location

Christiana Care Health System-Christiana Hospital

Newark, Delaware, 19718, United States

Location

Christiana Care Health System-Wilmington Hospital

Wilmington, Delaware, 19801, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

George Washington University Medical Center

Washington D.C., District of Columbia, 20037, United States

Location

Mount Sinai Comprehensive Cancer Center at Aventura

Aventura, Florida, 33180, United States

Location

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Indian River Medical Center

Vero Beach, Florida, 32960, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Atlanta VA Medical Center

Decatur, Georgia, 30033, United States

Location

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

Savannah, Georgia, 31405, United States

Location

Hawaii Cancer Care Inc - Waterfront Plaza