NCT04322643

Intermittent Checkpoint Inhibitor Therapy In Patients With Advanced Urothelial Carcinoma

A Phase II Study of Intermittent Checkpoint Inhibitor Therapy in Patients With Advanced Urothelial Carcinoma

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 4 (actual)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to test the safety and effectiveness of immunotherapy (checkpoint inhibitor therapy) in advanced bladder cancer when given intermittently. An unanswered question with the use of CPI (checkpoint inhibitor) is the duration of therapy required for optimal clinical benefit. In the absence of progressive disease or unacceptable toxicities, there are currently no specified criteria for treatment discontinuation. Strategies to reduce toxicity and maximize benefit require investigation. Thus, novel dosing schedules, early discontinuation considerations, and biomarkers of response are needed to identify patients who can sustain disease regression while off of therapy.

Detailed description

A phase II study design to investigate the use of any CPI on an intermittent dosing schedule. Patients with advanced urothelial carcinoma (aUC) who treatment refractory or cisplatin ineligible will receive CPI of choice as per standard dosing. Patients who have initial \>/=10% tumor burden reduction will discontinue the CPI until they experience a \>/=20% disease progression following 24 weeks +/- 4 weeks of immunotherapy, at which time CPI therapy will be restarted. All patients who do not meet criteria for the CPI intermittent phase of the study will be treated until unacceptable toxicity or RECIST-defined PD. Patients with RECIST-defined PD may continue CPI therapy at the discretion of the treating MD. These patients will continue with normal imaging every 12 weeks. In cases where a patient is continued on therapy after PD and develops subsequent PD (\> 20% increase in sum of target lesions compared to the initial PD tumor measurements, the patient will come off study). Patients who meet criteria for the intermittent phase (i.e., have \>/=10% tumor burden reduction) will not receive CPI therapy. Imaging will continue per protocol (every 12 weeks from the initial date they stopped CPI therapy). Patients who have RECIST defined PD on the intermittent phase should reinitiate CPI therapy. Patients who have a subsequent decrease in tumor burden \>/=10% can then restart CPI therapy as per protocol.

Conditions

• Urothelial Carcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Pembrolizumab 200 mg IV over 30 minutes every 3 weeks
DRUG	Atezolizumab	Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes)
DRUG	Durvalumab	Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks.
DRUG	Nivolumab	Nivolumab 480mg IV over 30 minutes every 4 weeks
DRUG	Avelumab	Avelumab 800 mg IV over 60 minutes every 2 weeks

Timeline

• Start date: 2020-03-23
• Primary completion: 2022-08-08
• Completion: 2023-04-17
• First posted: 2020-03-26
• Last updated: 2025-02-25
• Results posted: 2025-02-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study