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 : Recruiting
First Posted : May 22, 2018
Last Update Posted : December 7, 2018
Patients with muscle-invasive bladder cancer (MIBC) who can not receive 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 with cisplatin-ineligible MIBC (Stage T2-T4a, N0-N1, M0). Neoadjuvant treatment must start within 8 weeks of transurethral resection of the first 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.
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)|
|Estimated Enrollment :||43 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Cohort 1: Nivolumab alone. 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|
|Estimated Study Start Date :||December 2018|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||September 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 30 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
- Immunohistochemistry (IHC) Change [ Time Frame: 54 months ]Change in expression for pathologic partial and complete tumor response (defined by cystectomy pathologic staging <pT2N0 and pT0N0, respectively), in patients treated with nivolumab and nivolumab/lirilumab
- Peripheral Blood Mononuclear Cell (PBMC) T-Cell Subset Change [ Time Frame: 54 months ]%CD4+ T-cells will be assessed via flow cytometry and the change will be measured
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
|Contact: Carolyn Andrews, RNemail@example.com|
|United States, Texas|
|University of TX Southwestern||Recruiting|
|Dallas, Texas, United States, 75390|
|Contact: Allison Beaver Beaver 214-645-8788 firstname.lastname@example.org|
|Contact: Darren Fleming 214-648-8310 email@example.com|
|Principal Investigator: Kevin Courtney, MD|
|United States, Virginia|
|University of Virginia||Recruiting|
|Charlottesville, Virginia, United States, 22903|
|Contact: Jennifer Drake, RN 434-297-7782 firstname.lastname@example.org|
|Contact: Stacey Williams 434-243-8588 email@example.com|
|Principal Investigator: Robert Dreicer, MD|
|Study Chair:||Petros Grivas, MD, PhD||University of Washington|