NCT03464734

Pembrolizumab and Nab Paclitaxel in Patients With Metastatic Urothelial Carcinoma

An Open Label, Single-arm, Phase 2 Study of Pembrolizumab and Nanoparticle Albumin-bound Paclitaxel in Patients With Metastatic Urothelial Carcinoma After Chemotherapy Failure; the PEANUT Study

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (actual)
• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II, single-center study will assess the efficacy of pembrolizumab + nab-paclitaxel in patients who have metastatic urothelial tumor and do not respond to chemotherapy. The time between drug administration and progression of the disease will be assessed to determine if the drug will work.

Detailed description

In an open-label, single-arm, single-center, phase 2 trial, patients will receive pembrolizumab 200 mg intravenously (IV) on D1 and nab paclitaxel at the dose of 125 mg/m2 IV on D1 and D8. Cycles are repeated every 3 weeks until PD or onset of unacceptable toxicity. Key inclusion criteria are: predominant UC, failure of maximum 2 platinum-based CT regimens for metastatic disease (2nd-to-3rd line only). Neoadjuvant/adjuvant CT is counted if relapse occurred 6 months of the last CT cycle. Response is evaluated by RECIST criteria v.1.1 every 2 cycles. PD-L1 expression will be prospectively assessed on both immune cells (IC) and tumor cells at a centralized laboratory (National Cancer Institute Milano). Combined positivity score (CPS) for PD-L1 assessment will be used, as previously reported, and the 10% cutoff will be adopted for the analyses. The primary endpoint of the study is the progression-free survival (PFS). The target is to detect an improvement in the median PFS from 3.0 months (H0) to 5.0 months (H1). To achieve 90% power with a one-sided non-parametric test at the 10% significance level, we estimated that 64 patients must be accrued over 18 months, with follow-up duration of 12 months. PFS will be also analyzed according to the PD-L1 expression. Should the above investigation suggest that the treatment benefit is stronger in patients with CPS 10%, there is the option to expand this cohort up to a maximum of 50 patients. As such, we estimate 85% power to detect the target improvement in PFS. The decision of cohort expansion will rely on predictive power (PP) calculation: a PP 30% will be regarded as promising. Translational analyses will include multiparametric flow cytometry of blood samples, gene expression (RNA-seq, Illumina HiSeq) and mutation profiling of tumor samples (Ion Torrent Personal Genome Machine). These profiles will be matched with response to treatment and PFS/overall survival.

Conditions

• Metastatic Urothelial Carcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab and Nanoparticle Albumin-bound Paclitaxel	At study entry, patients will receive 2 cycles of pembrolizumab at the dose of 200 mg, intravenously in 30 min, on day 1 and nab-paclitaxel 125 mg/m2 intravenously in 30-40 min, on day 1 and 8.

Timeline

• Start date: 2019-01-16
• Primary completion: 2020-01-21
• Completion: 2020-01-21
• First posted: 2018-03-14
• Last updated: 2022-11-30

Locations

2 sites across 1 country: Italy