Pre-operative Immunotherapy in Stage II-III Urothelial Cancer
- Registration Number
- NCT04871594
- Lead Sponsor
- The Netherlands Cancer Institute
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nivolumab monotherapy Nivolumab Day 1: nivolumab 240 mg Day 22: nivolumab 240 mg Day 43: nivolumab 240 mg
- Primary Outcome Measures
Name Time Method Feasibility of pre-operative nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients At 12 weeks Percentage of patients that underwent surgery within 12 weeks after study start will be assessed
- Secondary Outcome Measures
Name Time Method Pathological complete response rates of nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients At 12 weeks Efficacy of nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients, assessed by the percentage of pathological complete response rate after cystectomy according to pathological response criteria
Toxicity of pre-operative nivolumab From first inusion untill 100 days after the last infusion with nivolumab All grade toxicities and immune-related toxicity of grade 3-4
Relapse free survival and overall survival From first infusion untill 3 years postoperative During follow-up, every 6 months untill 3 years postoperative, relapse free survival will be evaluated. Overall survival will be evaluated by phone calls
Monitor peri-surgical complications From surgery untill 90 days after surgery Peri-operative complications and morbidity will be graded according to the Clavien-Dindo classification
Translational: effects of nivolumab on the tumor microenvironment At 12 weeks Resistance mechanisms are explored by comparing immune (cell) infiltrates in responders and nonresponders in pre- and post treatment tissue \[Multiplex immunohistochemistry, RNA seq\]
Trial Locations
- Locations (2)
Radboud Universitair Medisch Centrum
🇳🇱Nijmegen, Netherlands
Antoni van Leeuwenhoek ziekenhuis
🇳🇱Amsterdam, Netherlands