Neoadjuvant Pembrolizumab for Muscle-invasive Urothelial Bladder Carcinoma
Status:
Recruiting
Trial end date:
2021-12-27
Target enrollment:
Participant gender:
Summary
Patients with T2-T4a N0 urothelial bladder carcinoma (UBC) with residual disease after
transurethral resection of the bladder (TURB, surgical opinion, cystoscopy or radiological
presence) will receive 3 cycles of pembrolizumab (MK-3475) at the dose of 200mg 3 weekly
prior to surgery (radical cystectomy). Cystectomy will be planned to be done within 3 weeks
of the last dose (accounting for a total of 9 weeks).
Computed tomography (CT) scan and fluorodeoxyglucose positron emission tomography
(FDG-PET)/CT scan will be done during screening and before surgery. After cystectomy,
patients with the evidence of pathologic stage T3-4 (pT3-4) and/or pathologically
node-positive disease will be managed according to local guidelines. Further anti
programmed-death (PD)-1 or anti PD-ligand 1 (PD-L1) therapy will not be given
post-operatively.
PD-L1 status will be centralized and assessed on TURB specimen using an anti-PD-L1 antibody
(Ab) and a prototype immunohistochemical (IHC) assay. PD-L1 positivity will be defined as any
staining in the stroma or in ≥1% of tumor cells.
Pathologic complete response (pCR) is the primary endpoint. All patients enrolled who receive
at least 1 cycle of study drug will be includes in the intention-to-treat (ITT) analysis.
The alternative hypothesis (H1) is pCR ≥20% and null hypothesis (H0) pCR≤10%. A 2-stage
design will be used to estimate the number of pts required. Out of 90 pts overall, with the
first stage of 49 pts, ≥6 pCR will be required in the first stage, and ≥13 pCR in the whole
study population (80% power and a 2-sided test of significance at the 10% level).
Correlative research on tissue/blood samples will include immune-cell profiling in tumor and
blood during Pembrolizumab, cytokine assessment, and molecular profiling of tumor samples.
Phase:
Phase 2
Details
Lead Sponsor:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano