A Phase 1b Trial in Stage II-III Urothelial Cancer to Explore Pre-operative Immunotherapy
Overview
- Phase
- Phase 1
- Intervention
- Nivolumab
- Conditions
- Urothelial Carcinoma
- Sponsor
- The Netherlands Cancer Institute
- Enrollment
- 15
- Locations
- 2
- Primary Endpoint
- Feasibility of pre-operative nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a phase 1b feasibility study of pre-operative immunotherapy in PD-L1 positive resectable stage II-III urothelial cancer patients. This study can be adapted or expanded based on the results obtained.
Detailed Description
This is a phase 1b feasibility study of pre-operative immunotherapy in PD-L1 positive resectable stage II-III urothelial cancer patients. Urothelial cancer patients will be included that are diagnosed with either: * cT2-4aN0M0 OR * cT1-4aN1-3M0 PD-L1 status will be determined. When PD-L1 CPS is ≥10%, patients will be treated with three cycles nivolumab 240 mg, q3wk, on day 1, 22, 43. The primary endpoint is feasibility of pre-operative nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients. After surgery, patients attend study visits at day 8 and at day 29. Their final study visit for physical examination and laboratory testing is at day 57 (+/- 7 days), which is scheduled to anticipate late-onset adverse events. 90 days postoperative, surgical complications according to the Clavien-dindo classification will be evaluated. Thereafter, patients will be followed according to standard clinical guidelines. Tumor biopsies/material preservation is required at baseline and during surgery. Main secondary endpoints are: * To identify pathological complete response rates of nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients * To describe immune-related grade 3/4 and all grade toxicities * To describe RFS and OS * Translational: Effects of immunotherapy on the tumor microenvironment based on RNA signatures and changes in immune infiltrates between baseline and resection.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Nivolumab monotherapy
Day 1: nivolumab 240 mg Day 22: nivolumab 240 mg Day 43: nivolumab 240 mg
Intervention: Nivolumab
Outcomes
Primary Outcomes
Feasibility of pre-operative nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients
Time Frame: At 12 weeks
Percentage of patients that underwent surgery within 12 weeks after study start will be assessed
Secondary Outcomes
- Pathological complete response rates of nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients(At 12 weeks)
- Toxicity of pre-operative nivolumab(From first inusion untill 100 days after the last infusion with nivolumab)
- Relapse free survival and overall survival(From first infusion untill 3 years postoperative)
- Monitor peri-surgical complications(From surgery untill 90 days after surgery)
- Translational: effects of nivolumab on the tumor microenvironment(At 12 weeks)