Phase Ib Feasibility Trial of Neoadjuvant Nivolumab/Lirilumab in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer (PrE0807)
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|ClinicalTrials.gov Identifier: NCT03532451|
Recruitment Status : Active, not recruiting
First Posted : May 22, 2018
Last Update Posted : March 25, 2021
Patients with muscle-invasive bladder cancer (MIBC) who can not receive cisplatin or refuse cisplatin therapy will receive nivolumab or nivolumab/lirilumab before a planned surgical procedure called a radical cystectomy (RC) to remove the bladder.
Nivolumab works by attaching to and blocking a molecule called Programmed Death-1 (PD-1). Lirilumab attaches to and blocks a group of molecules called Killer Cell Immunoglobulin-Like Receptor (KIR). PD-1 and KIR are proteins present mainly on immune system cells, and each controls part of the immune system by shutting it down. It is hoped that by binding to and inactivating these proteins, these drugs can enhance the body's ability to detect, attack and destroy cancer cells.
The purpose of this research study is to see whether nivolumab alone or combination of nivolumab and lirilumab given before surgery is effective in treating people who have bladder cancer, and to examine the side effects, good and bad, associated with nivolumab and lirilumab.
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer||Drug: Nivolumab Drug: Nivolumab/Lirilumab||Phase 1|
Bladder cancer (BC) is the 6th most common malignancy in the United States with an estimated 79,030 new cases and 16,870 deaths in 2017. It is the 4th most common cancer in men and there are presently >500,000 BC patients alive in the US. It accounts for about 5% of all new cancers in the US. It is also the most expensive cancer to treat from diagnosis to death. Almost a third of BC patients present with MIBC.
This is a Phase Ib open-label clinical trial for patients that are either cisplatin-ineligible or refuse cisplatin-based chemotherapy and have MIBC (T2-T4a, N0-N1, M0).Neoadjuvant treatment must start within 10 weeks of transurethral resection of the most recent transurethral resection of bladder tumor (TURBT) that showed muscularis propria invasion.
Patients must have sufficient baseline tumor tissue. Tumor tissue content for CD8+ T-cell density assessment must be qualified as sufficient (≥ 20% tumor content in the specimen) for analysis and must be documented by the local pathologist prior to registration.
The first 12 patients will be enrolled into Cohort 1 and treated with nivolumab before a planned RC (Completed November 20, 2019).
In the absence of the occurrence of high rate of treatment related Adverse Events (AEs) with nivolumab, the study will proceed with enrollment into Cohort 2 with the combination of nivolumab/lirilumab before a planned RC.
Each group will receive a total of 2 doses (week 0 and 4) of nivolumab (Cohort 1) or nivolumab/lirilumab (Cohort 2) therapy followed by RC with bilateral (standard or extended) pelvic lymph node dissection (PLND).
Mandatory tumor tissue at Screening (archived tumor tissue from Transurethral Resection of Bladder Tumor [TURBT] may be used) and at time of RC. Peripheral blood and urine samples are also required.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||43 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Cohort 1: Nivolumab alone (Completed November 20, 2019). In the absence of the occurrence of high rate of treatment related adverse events, the study will proceed with enrollment into Cohort 2: Nivolumab/Lirilumab.|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib Feasibility Trial of Neoadjuvant Nivolumab/Lirilumab in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer|
|Actual Study Start Date :||March 22, 2019|
|Actual Primary Completion Date :||November 27, 2020|
|Estimated Study Completion Date :||November 2022|
Experimental: Cohort 1: Nivolumab
Nivolumab 480 mg IV on week 0 and week 4
Nivolumab 480 mg intravenously (IV) over approximately 30 minutes every 4 weeks for 2 neo-adjuvant doses (week 0 and 4) followed by RC with bilateral (standard or extended) PLND as soon as possible but within 6 weeks after the last neoadjuvant infusion.
Other Name: Opdivo
Experimental: Cohort 2: Nivolumab/Lirilumab
Nivolumab 480 mg IV and Lirilumab 240 mg on week 0 and week 4
Nivolumab 480 mg IV over approximately 60 minutes every 4 weeks for 2 neo-adjuvant doses (week 0 and 4) with at least a 30 minute rest between infusions followed by lirilumab 240 mg IV over approximately 60 minutes every 4 weeks for 2 neo-adjuvant doses (week 0 and 4) followed by RC with bilateral (standard or extended) PLND as soon as possible but within 6 weeks after the last neoadjuvant infusion.
- Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE V5.0 [ Time Frame: 30 months ]Number of patients with Grade 3 or higher adverse events (AEs) related to nivolumab and nivolumab/lirilumab
- Change in CD8+ Tumor-Infiltrating Lymphocytes (TIL) Density [ Time Frame: 54 months ]Change (#) in CD8+ TIL density from pre-treatment TURBT to post-treatment RC tissues in patients treated with nivolumab and nivolumab/lirilumab
- Percent Change in CD8+ TIL Density [ Time Frame: 54 months ]Percent change in CD8+ TIL density from pre-treatment TURBT to post-treatment RC tissues in patients treated with nivolumab and nivolumab/lirilumab
- Number of Patients unable to undergo RC [ Time Frame: 30 months ]Number of patients in each cohort who do not get RC within 6 weeks after completion of neoadjuvant treatment related to treatment-related AEs
- Complete Response Rate [ Time Frame: 30 months ]Measured by pathologic complete (pT0N0) and partial (<pT2N0) response rate at time of RC in the two cohorts
- Recurrence-Free Survival (RFS) [ Time Frame: 54 months ]Rate of RFS at the two-year time point from the time of registration in patients treated with nivolumab and nivolumab/lirilumab
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): NCT03532451
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, New York|
|Montefiore Medical Center|
|Bronx, New York, United States, 10461|
|Icahn School of Medicine at Mount Sinai|
|New York, New York, United States, 10029|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|United States, Texas|
|University of TX Southwestern|
|Dallas, Texas, United States, 75390|
|United States, Virginia|
|University of Virginia|
|Charlottesville, Virginia, United States, 22903|
|United States, Washington|
|University of Washington|
|Seattle, Washington, United States, 98109|
|Study Chair:||Petros Grivas, MD, PhD||University of Washington|