Atezolizumab in Treating Patients With Recurrent BCG-Unresponsive Non-muscle Invasive Bladder Cancer
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|ClinicalTrials.gov Identifier: NCT02844816|
Recruitment Status : Recruiting
First Posted : July 26, 2016
Last Update Posted : June 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: Atezolizumab||Phase 2|
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.
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.
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.
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 (Clinical Trial)|
|Estimated Enrollment :||162 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Atezolizumab in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer|
|Actual Study Start Date :||February 7, 2017|
|Estimated Primary Completion Date :||April 1, 2021|
|Estimated Study Completion Date :||April 1, 2021|
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.
- Complete response (CR) rate in the subset of patients with carcinoma in situ (CIS) based on biopsy [ Time Frame: At 25 weeks ]Will be estimated to within +/- 12% (95% confidence interval).
- Event-free survival (EFS) [ Time Frame: From date of registration to first documentation of event, assessed up to 18 months ]The 18-month EFS estimate will be obtained using the method of Kaplan and Meier, and the Greenwood formula will be used to estimate the variance. A 90% confidence interval will be estimated for the 18-month EFS estimate. The 99% confidence interval around the 18 month EFS Kaplan-Meier estimate will be constructed.
- Event-free survival (EFS) in the Ta/T1 subset [ Time Frame: 18 months ]Will estimate for the subset of patients with papillary cancer (Ta/T1).
- Progression-free survival (PFS) [ Time Frame: From time of registration to time of first documentation progression or death due to any cause, assessed up to 5 years ]Progression will be defined as biopsy proven muscle invasive disease stage >= T2, nodal or distant metastasis and estimated using Kaplan-Meier.
- Cystectomy-free survival [ Time Frame: Up to 5 years ]Estimated using Kaplan-Meier.
- Bladder cancer specific survival [ Time Frame: From date of registration to date of death due to bladder cancer, assessed up to 5 years ]Estimated using Kaplan-Meier.
- Overall survival [ Time Frame: From date of registration to date of death due to any cause, assessed up to 5 years ]Estimated using Kaplan-Meier.
- Incidence of adverse events [ Time Frame: Up to 18 months ]Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Qualitative and quantitative toxicity assessment will be provided using CTCAE reporting. Will be estimated to within +/- 9% (95% confidence interval).
- Recurrence in all patients [ Time Frame: Up to 5 years ]Will estimate the level of agreement between local and central pathology review.
- CR for the CIS subset [ Time Frame: Up to 5 years ]Will estimate the level of agreement between local and central pathology review.
- PD-L1 and CD8 expression [ Time Frame: Up to 5 years ]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.
- Immune signature expression [ Time Frame: Up to 5 years ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02844816
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|Principal Investigator:||Peter C Black||Southwest Oncology Group|