Nivolumab and Radiation Therapy in Treating Patients With Localized/Locally Advanced Urothelial Bladder Cancer Ineligible for Chemotherapy
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|ClinicalTrials.gov Identifier: NCT03421652|
Recruitment Status : Recruiting
First Posted : February 5, 2018
Last Update Posted : May 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|Stage II Bladder Urothelial Carcinoma AJCC v6 and v7 Stage III Bladder Urothelial Carcinoma AJCC v6 and v7 Stage IV Bladder Urothelial Carcinoma AJCC v7||Drug: Nivolumab Radiation: Radiation||Phase 2|
I. To compare the 12-month rate of progression-free survival (PFS) achieved with the combination of nivolumab, a programmed death (PD-1) inhibitor, and radiation therapy in localized/locally advanced urothelial cancer patients, who are chemotherapy ineligible, to a historical control reference 12-month PFS rate.
I. To assess the toxicity of concurrent nivolumab and radiation therapy in urothelial cancer.
II. To determine overall response rate (ORR). III. To determine metastasis-free survival (MFS). IV. To determine overall survival (OS). V. To evaluate the quality of life and bladder functioning during and after the therapy.
VI. To explore the relationships of PD-1 expression, PDL-1 expression, and the Th1/Th2 cytokine ratio to clinical outcomes (response, PFS, MFS, and OS).
Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 14 days (2 weeks) for up to 14 courses (6 months) in the absence of disease progression or unacceptable toxicity. Beginning 3 days of course 1, patients undergo radiation therapy over 32-35 on weeks 1, 3, 5, 7 and 9.
After completion of study treatment, patients are followed up every 3 months for 12 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Concurrent Nivolumab in Urothelial Bladder Cancer With Radiation Therapy in Localized/Locally Advanced Disease for Chemotherapy Ineligible Patients [NUTRA]|
|Actual Study Start Date :||April 24, 2018|
|Estimated Primary Completion Date :||January 2021|
|Estimated Study Completion Date :||January 2021|
Experimental: Treatment (nivolumab, radiation therapy)
Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days (2 weeks) for up to 14 courses (6 months) in the absence of disease progression or unacceptable toxicity. Beginning 3 days of course 1, patients undergo radiation therapy over 32-35 on weeks 1, 3, 5, 7 and 9.
Beginning 3 days of course 1, patients undergo radiation therapy over 32-35 on weeks 1, 3, 5, 7 and 9.
- Progression-free survival (PFS) [ Time Frame: From date of registration to date of first documented disease relapse/progression, or death from urothelial cancer whichever occurs first, assessed up to 12 months ]PFS distribution will be summarized with the Kaplan-Meier (K-M) survivorship estimate. A graph of the K-M curve for PFS will be generated along with the Hall-Wellner 95% confidence band, and a display of the number of patients at risk at several time points, below the X-axis. Summary statistics (12-month PFS rate, median PFS, etc.) will be calculated from the K-M life table, each one with its respective 95% confidence interval (CI).
- Incidence of adverse events graded per Common Terminology Criteria for Adverse Events version 4.0. [ Time Frame: Up to 12 months ]Frequency distributions of each toxicity type by severity grade will be generated. For a given grade(s), the point estimate of the toxicity rate will be computed, along with its 95% (Wilson type) CI.
- Overall response rate (ORR) [ Time Frame: Up to 12 months ]ORR will be estimated among the response evaluable patients and among all patients. Frequency distributions of best response will be generated for each of those sets of patients. The point estimate of the ORR will be computed, along with its 95% (Wilson type) CI.
- Metastasis-free survival (MFS) [ Time Frame: From registration to the appearance of metastases or cancer related death, assessed up to 12 months ]Summary statistics of MFS will be calculated from the K-M life tables. K-M graphs of the censored MFS distributions will also be generated.
- Overall survival (OS) [ Time Frame: From date of registration to death or last follow up, assessed up to 12 months ]Summary statistics of OS will be calculated from the K-M life tables. K-M graphs of the censored OS distributions will also be generated.
- Quality of life (QOL) and bladder functioning questionnaires assessment [ Time Frame: Up to 12 months ]The QOL score will be measured pre therapy, during therapy and after therapy to compare the changes.
- PD-1 and PDL-1 expression analysis using immunohistochemistry (IHC) [ Time Frame: Up to 12 months ]PDL-1 status will be checked on pre-therapy tumor tissue and will be correlated with the primary endpoint.
- Th1/Th2 cytokine ratio analysis [ Time Frame: Up to 12 months ]The continuous markers (e.g., tumor infiltrating lymphocyte [TIL]s, Th1/Th2 cytokine ratio, etc.) will be summarized with standard descriptive statistics. These descriptive analyses of the serum markers will be performed for each time point at which the each marker is determined. Response (CR/PR vs not) will be modeled as a function of a dichotomized version of pre-study the continuous (ungrouped) markers (e.g., TILs from tissue, and the Th1/Th2 cytokine ratio from serum). The statistical goal of these exploratory analyses is to obtain the point and 95% CI estimates of the OR, and to simply determine the direction and approximate magnitude of these associations for use in planning a subsequent study. Censored PFS will be modeled as a function of a dichotomized version of the continuous (ungrouped) markers (e.g., TILs from tissue, and the Th1/Th2 cytokine ratio using Cox modelling strategy.
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): NCT03421652
|Contact: Ulka N. Vaishampayan, M.D.||(313) firstname.lastname@example.org|
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Clinical Trials Office 800-527-6266 email@example.com|
|Principal Investigator: Ulka N. Vaishampayan, M.D.|
|Sub-Investigator: Joseph Fontana, M.D.|
|Sub-Investigator: Elisabeth I. Heath, M.D.|
|Sub-Investigator: Jordan Maier, M.D.|
|Sub-Investigator: Steven Miller, M.D.|
|Sub-Investigator: Michael Dominello, M.D.|
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Saby George, M.D., FACP 716-845-3863 Saby.George@RoswellPark.org|
|Principal Investigator:||Ulka N. Vaishampayan, M.D.||Barbara Ann Karmanos Cancer Institute|