NCT03532451

Phase Ib Feasibility Trial of Neoadjuvant Nivolumab/Lirilumab in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: PrECOG, LLC. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Bladder Cancer

Interventions

Type	Name	Description
DRUG	Nivolumab	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.
DRUG	Nivolumab/Lirilumab	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.

Timeline

• Start date: 2019-03-22
• Primary completion: 2020-11-27
• Completion: 2022-10-05
• First posted: 2018-05-22
• Last updated: 2024-09-19
• Results posted: 2021-09-01

Locations

8 sites across 1 country: United States

Regulatory

• FDA-regulated drug study